Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy.

PubMed

Fallil, Zianka; Pardoe, Heath; Bachman, Robert; Cunningham, Benjamin; Parulkar, Isha; Shain, Catherine; Poduri, Annapurna; Knowlton, Robert; Kuzniecky, Ruben

2015-10-01

Periventricular nodular heterotopia (PVNH) is a malformation of cortical development due to impaired neuronal migration resulting in the formation of nodular masses of neurons and glial cells in close proximity to the ventricular walls. We report the clinical characteristics of the largest case series of FLNA-negative patients with seizures and bilateral periventricular heterotopia. Participants were recruited through the Epilepsy Phenome/Genome Project (EPGP), a multicenter collaborative effort to collect detailed phenotypic data and DNA on a large number of individuals with epilepsy, including a cohort with symptomatic epilepsy related to PVNH. Included subjects had epilepsy, and MRI confirmed bilateral PVNH. Magnetic resonance imaging studies were visually and quantitatively reviewed to investigate the topographic extent of PVNH, symmetry, and laterality. We analyzed data on 71 patients with bilateral PVNH. The incidence of febrile seizures was 16.6%. There was at least one other family member with epilepsy in 36.9% of this population. Developmental delay was present in 21.8%. Focal onset seizures were the most common type of seizure presentation (79.3%). High heterotopia burden was strongly associated with female gender and trigonal nodular localization. There was no evidence for differences in brain volume between PVNH subjects and controls. No relationship was observed between heterotopic volume and gender, developmental delay, location of PVNH, ventricular or cerebellar abnormalities, laterality of seizure onset, age at seizure onset, and duration of epilepsy. A direct correlation was observed between high heterotopia burden, female gender, and trigonal location in this large cohort of FLNA-negative bilateral PVNH patients with epilepsy. Quantitative MRI measurements indicated that this correlation is based on the diffuse nature of the heterotopic nodules rather than on the total volume of abnormal heterotopic tissue. Copyright © 2015 Elsevier Inc. All rights reserved.

Phelan-McDermid syndrome presenting with developmental delays and facial dysmorphisms.

PubMed

Kim, Yoon-Myung; Choi, In-Hee; Kim, Jun Suk; Kim, Ja Hye; Cho, Ja Hyang; Lee, Beom Hee; Kim, Gu-Hwan; Choi, Jin-Ho; Seo, Eul-Ju; Yoo, Han-Wook

2016-11-01

Phelan-McDermid syndrome is a rare genetic disorder caused by the terminal or interstitial deletion of the chromosome 22q13.3. Patients with this syndrome usually have global developmental delay, hypotonia, and speech delays. Several putative genes such as the SHANK3 , RAB , RABL2B , and IB2 are responsible for the neurological features. This study describes the clinical features and outcomes of Korean patients with Phelan-McDermid syndrome. Two patients showing global developmental delay, hypotonia, and speech delay were diagnosed with Phelan-McDermid syndrome via chromosome analysis, fluorescent in situ hybridization, and multiplex ligation-dependent probe amplification analysis. Brain magnetic resonance imaging of Patients 1 and 2 showed delayed myelination and severe communicating hydrocephalus, respectively. Electroencephalography in patient 2 showed high amplitude spike discharges from the left frontotemporoparietal area, but neither patient developed seizures. Kidney ultrasonography of both the patients revealed multicystic kidney disease and pelviectasis, respectively. Patient 2 experienced recurrent respiratory infections, and chest computed tomography findings demonstrated laryngotracheomalacia and bronchial narrowing. He subsequently died because of heart failure after a ventriculoperitoneal shunt operation at 5 months of age. Patient 1, who is currently 20 months old, has been undergoing rehabilitation therapy. However, global developmental delay was noted, as determines using the Korean Infant and Child Development test, the Denver developmental test, and the Bayley developmental test. This report describes the clinical features, outcomes, and molecular genetic characteristics of two Korean patients with Phelan-McDermid syndrome.

A novel CDKL5 mutation in a 47,XXY boy with the early-onset seizure variant of Rett syndrome.

PubMed

Sartori, Stefano; Di Rosa, Gabriella; Polli, Roberta; Bettella, Elisa; Tricomi, Giovanni; Tortorella, Gaetano; Murgia, Alessandra

2009-02-01

Mutations of the cyclin-dependent kinase-like 5 gene (CDKL5), reported almost exclusively in female subjects, have been recently found to be the cause of a phenotype overlapping Rett syndrome with early-onset epileptic encephalopathy. We describe the first CDKL5 mutation detected in a male individual with 47,XXY karyotype. This previously unreported, de novo, mutation truncates the large CDKL5 COOH-terminal region, thought to be crucial for the proper sub-cellular localization of the CDKL5 protein. The resulting phenotype is characterized by a severe early-onset epileptic encephalopathy, global developmental delay, and profound intellectual and motor impairment with features reminiscent of Rett syndrome. In light of the data presented we discuss the possible phenotypic modulatory effects of the supernumerary wild type X allele and pattern of X chromosome inactivation and stress the importance of considering the causal involvement of CDKL5 in developmentally delayed males with early-onset seizures. (c) 2009 Wiley-Liss, Inc.

Prevalence of seizures in children infected with human immunodeficiency virus.

PubMed

Samia, Pauline; Petersen, Reneva; Walker, Kathleen G; Eley, Brian; Wilmshurst, Jo M

2013-03-01

A retrospective study of 354 human immunodeficiency virus (HIV)-infected patients identified a subgroup of 27 children with seizures (7.6%, 95% confidence interval: 5.1%-10.9%). Of the total group, 13% (n = 46) had identifiable neurologic deficits and 30% (n = 107) had developmental delay. Both observations were significantly more frequent in the subgroup of patients with seizures (P < .001). The median age of patients with seizures was 20 months (range, 8-87 months) and the median baseline CD4 percentage was 13.5% (interquartile range, 8%-23%). Seizures were treated with sodium valproate (n = 11), phenobarbital (n = 3), diazepam (n = 2), lamotrigine (n = 1), and carbamazepine (n = 1). Combination therapy was required for 5 children. Suboptimal valproic acid levels were recorded for 3 patients. When resources are available, antiepileptic drug level monitoring is advised for children who require both antiepileptic and antiretroviral medications to facilitate optimal seizure management.

Brief Report: Autistic Symptoms, Developmental Regression, Mental Retardation, Epilepsy, and Dyskinesias in CNS Folate Deficiency

ERIC Educational Resources Information Center

Moretti, Paolo; Peters, Sarika U.; del Gaudio, Daniela; Sahoo, Trilochan; Hyland, Keith; Bottiglieri, Teodoro; Hopkin, Robert J.; Peach, Elizabeth; Min, Sang Hee; Goldman, David; Roa, Benjamin; Bacino, Carlos A.; Scaglia, Fernando

2008-01-01

We studied seven children with CNS folate deficiency (CFD). All cases exhibited psychomotor retardation, regression, cognitive delay, and dyskinesia; six had seizures; four demonstrated neurological abnormalities in the neonatal period. Two subjects had profound neurological abnormalities that precluded formal behavioral testing. Five subjects…

Clinical features and outcome of 6 new patients carrying de novo KCNB1 gene mutations.

PubMed

Marini, Carla; Romoli, Michele; Parrini, Elena; Costa, Cinzia; Mei, Davide; Mari, Francesco; Parmeggiani, Lucio; Procopio, Elena; Metitieri, Tiziana; Cellini, Elena; Virdò, Simona; De Vita, Dalila; Gentile, Mattia; Prontera, Paolo; Calabresi, Paolo; Guerrini, Renzo

2017-12-01

To describe electroclinical features and outcome of 6 patients harboring KCNB1 mutations. Clinical, EEG, neuropsychological, and brain MRI data analysis. Targeted next-generation sequencing of a 95 epilepsy gene panel. The mean age at seizure onset was 11 months. The mean follow-up of 11.3 years documented that 4 patients following an infantile phase of frequent seizures became seizure free; the mean age at seizure offset was 4.25 years. Epilepsy phenotypes comprised West syndrome in 2 patients, infantile-onset unspecified generalized epilepsy, myoclonic and photosensitive eyelid myoclonia epilepsy resembling Jeavons syndrome, Lennox-Gastaut syndrome, and focal epilepsy with prolonged occipital or clonic seizures in each and every one. Five patients had developmental delay prior to seizure onset evolving into severe intellectual disability with absent speech and autistic traits in one and stereotypic hand movements with impulse control disorder in another. The patient with Jeavons syndrome evolved into moderate intellectual disability. Mutations were de novo, 4 missense and 2 nonsense, 5 were novel, and 1 resulted from somatic mosaicism. KCNB1 -related manifestations include a spectrum of infantile-onset generalized or focal seizures whose combination leads to early infantile epileptic encephalopathy including West, Lennox-Gastaut, and Jeavons syndromes. Long-term follow-up highlights that following a stormy phase, seizures subside or cease and treatment may be eased or withdrawn. Cognitive and motor functions are almost always delayed prior to seizure onset and evolve into severe, persistent impairment. Thus, KCNB1 mutations are associated with diffuse brain dysfunction combining seizures, motor, and cognitive impairment.

Diagnostic delays in children with early-onset epilepsy: impact, reasons, and opportunities to improve care

PubMed Central

Berg, Anne T.; Loddenkemper, Tobias; Baca, Christine B.

2014-01-01

Purpose Delayed diagnosis of early-onset epilepsy is a potentially important and avoidable complication in epilepsy care. We examined the frequency of diagnostic delays in young children with newly presenting epilepsy, their developmental impact, and reasons for delays. Methods Children who developed epilepsy before their third birthday were identified in a prospective community-based cohort. An interval ≥1 month from second seizure to diagnosis was considered a delay. Testing of development at baseline and for up to three years after and of IQ 8–9 years later was performed. Detailed parental baseline interview accounts and medical records were reviewed to identify potential reasons for delays. Factors associated with delays included the parent, child, pediatrician, neurologist, and scheduling. Results Diagnostic delays occurred in 70/172 (41%) children. Delays occurred less often if children had received medical attention for the first seizure (p<0.0001), previously had neonatal or febrile seizures (p=0.02), had only convulsions before diagnosis (p=0.005) or had a college-educated parent (p=0.01). A ≥1 month diagnostic delay was associated with an average 7.4 point drop (p=0.02) in the Vineland Scales of Adaptive Behavior motor score. The effect was present at diagnosis, persisted for at least three years, and was also apparent in IQ scores 8–9 years later which were lower in association with a diagnostic delay by 8.4 points (p=0.06) for processing speed up to 14.5 points (p=0.004) for full scale IQ, after adjustment for parental education and other epilepsy-related clinical factors. Factors associated with delayed diagnosis included parents not recognizing events as seizures (N=47), pediatricians missing or deferring diagnosis (N=15), neurologists deferring diagnosis (N=7), and scheduling problems (N=11). Significance Diagnostic delays occur in many young children with epilepsy. They are associated with substantial decrements in development and IQ later in childhood. Several factors influence diagnostic delays and may represent opportunities for intervention and improved care. PMID:24313635

Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis.

PubMed

Trump, Natalie; McTague, Amy; Brittain, Helen; Papandreou, Apostolos; Meyer, Esther; Ngoh, Adeline; Palmer, Rodger; Morrogh, Deborah; Boustred, Christopher; Hurst, Jane A; Jenkins, Lucy; Kurian, Manju A; Scott, Richard H

2016-05-01

We sought to investigate the diagnostic yield and mutation spectrum in previously reported genes for early-onset epilepsy and disorders of severe developmental delay. In 400 patients with these disorders with no known underlying aetiology and no major structural brain anomaly, we analysed 46 genes using a combination of targeted sequencing on an Illumina MiSeq platform and targeted, exon-level microarray copy number analysis. We identified causative mutations in 71/400 patients (18%). The diagnostic rate was highest among those with seizure onset within the first two months of life (39%), although overall it was similar in those with and without seizures. The most frequently mutated gene was SCN2A (11 patients, 3%). Other recurrently mutated genes included CDKL5, KCNQ2, SCN8A (six patients each), FOXG1, MECP2, SCN1A, STXBP1 (five patients each), KCNT1, PCDH19, TCF4 (three patients each) and ATP1A3, PRRT2 and SLC9A6 (two patients each). Mutations in EHMT1, GABRB3, LGI1, MBD5, PIGA, UBE3A and ZEB2 were each found in single patients. We found mutations in a number of genes in patients where either the electroclinical features or dysmorphic phenotypes were atypical for the identified gene. In only 11 cases (15%) had the clinician sufficient certainty to specify the mutated gene as the likely cause before testing. Our data demonstrate the considerable utility of a gene panel approach in the diagnosis of patients with early-onset epilepsy and severe developmental delay disorders., They provide further insights into the phenotypic spectrum and genotype-phenotype correlations for a number of the causative genes and emphasise the value of exon-level copy number testing in their analysis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

CDKL5 variant in a boy with infantile epileptic encephalopathy: case report.

PubMed

Wong, Virginia Chun-Nei; Kwong, Anna Ka-Yee

2015-04-01

A Chinese boy presented at 18 months with intractable epilepsy, developmental delay and autistic features. He had multiple seizure types, including absence, myoclonic seizures, limb spasm and tonic seizures. His seizures were finally controlled at 3 years of age with clonazepam and a short course of chloral hydrate incidentally given for his insomnia. Subsequently, he had improvement in his communication skills. A novel hemizygous missense variant (c.1649G>A; p.R550Q) in exon 12 of CDKL5 gene was detected for him, his asymptomatic mother and elder sister. His phenotype is less severe than other male cases. We recommend screening CDKL5 for boys with pharmarco-resistant epilepsy and a trial of benzodiazepines for Infantile Epileptic Encephalopathy (IEE). Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Successful treatment of migrating partial seizures in Wolf-Hirschhorn syndrome with bromide.

PubMed

Itakura, Ayako; Saito, Yoshiaki; Nishimura, Yoko; Okazaki, Tetsuya; Ohno, Koyo; Sejima, Hitoshi; Yamamoto, Toshiyuki; Maegaki, Yoshihiro

2016-08-01

A girl with mild psychomotor developmental delay developed right or left hemiclonic convulsion at 10months of age. One month later, clusters of hemiclonic or bilateral tonic seizures with eyelid twitching emerged, resulting in status epilepticus. Treatment with phenobarbital and potassium bromide completely terminated the seizures within 10days. Ictal electroencephalography revealed a migrating focus of rhythmic 3-4Hz waves from the right temporal to right frontal regions and then to the left frontal regions. Genetic analysis was conducted based on the characteristic facial appearance of the patient, which identified a 2.1-Mb terminal deletion on chromosome 4p. This is the first case of Wolf-Hirschhorn syndrome complicated by epilepsy with migrating partial seizures. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

A rare case of short stature: Say Meyer syndrome.

PubMed

Karthik, T S; Prasad, N Rajendra; Rani, P Radha; Maheshwari, Rushikesh; Reddy, P Amaresh; Chakradhar, B V S; Menon, Bindu

2013-10-01

Say Meyer syndrome is rare X linked condition characterized by developmental delay, short stature and metopic suture synostosis. We are reporting a case of Say Meyer syndrome presented to our hospital for short stature and developmental delay at age 3½ years. A 3½-year-old boy presented to our hospital for decreased growth velocity from the age of 1 year. History revealed the boy had a birth weight of 2.3 kg, had an episode of seizures in the neonatal period. He was born to non-consanguineous marriage. He had global developmental delay and there was a lack of bowel and bladder control. History did not reveal any hearing or visual impairment. No history of any chronic systemic illnesses. Magnetic resonance imaging (MRI) brain revealed mild diffuse frontotemporal atrophy with multiple irregular gliotic areas in bilateral frontal lobes. Diffuse white matter volume loss in bilateral cerebral hemispheres. Diffuse thinning of corpus callosum. Diffuse periventricular hyper intensity on T2W and fluid attenuated inversion recovery sequences. Say Meyer syndrome is rare X linked condition characterized by developmental delay, short stature and metopic suture synostosis. Characteristic MRI brain findings include diffuse frontotemporal atrophy with multiple gliotic areas in frontal lobes. Diffuse white matter volume loss in bilateral cerebral hemispheres.

CDC Kerala 15: Developmental Evaluation Clinic (2-10 y)--developmental diagnosis and use of home intervention package.

PubMed

Nair, M K C; Lakshmi, M A; Latha, S; Lakshmi, Geetha; Harikumaran Nair, G S; Bhaskaran, Deepa; George, Babu; Leena, M L; Russell, Paul Swamidhas Sudhakar

2014-12-01

To describe the last 5 years' experience of Child Development Centre (CDC), Kerala Developmental Evaluation Clinic II for children between 2 and 10 y, referred for suspicion of developmental lag in the preschool years and scholastic difficulty in the primary classes with specific focus on developmental profile and the experience of the home based intervention package taught to the mothers. A team of evaluators including developmental therapist, preschool teacher with special training in clinical child development, speech therapist, special educator, clinical psychologist and developmental pediatrician assessed all the children referred to CDC Kerala. Denver Developmental Screening Test (DDST-II), Vineland Social Maturity Scale (VSMS) and Intelligent Quotient (IQ) tests were administered to all children below 6 y and those above 6 with apparent developmental delay. Speech/delay (35.9%), behavior problem (15.4%), global delay/ intellectual disability (15.4%), learning problem (10.9%), pervasive developmental disorders (7.7%), seizure disorder (1.7%), hearing impairment (0.7%), and visual impairment (0.7%) were the clinical diagnosis by a developmental pediatrician. Each child with developmental problem was offered a home based intervention package consisting of developmental therapy and special education items, appropriate to the clinical diagnosis of the individual child and the same was taught to the mother. The experience of conducting the developmental evaluation clinic for children between 2 and 10 y has shown that a team consisting of developmental therapist, speech therapist, preschool teacher, special educator, clinical child psychologist and developmental pediatrician, using appropriate test results of the child could make a clinical diagnosis good enough for providing early intervention therapy using a home based intervention package.

Afebrile seizure subsequent to initial febrile seizure.

PubMed

Fallah, Razieh; Razieh, Fallah; Akhavan Karbasi, Sedighah; Sedighah, Akhavan Karbasi; Golestan, Motahhareh; Motahhareh, Golestan

2012-05-01

Febrile seizure (FS) is the most common paediatric neurological problem. The purpose of this study was to determine the frequency of afebrile seizures subsequent to FS in children with initial FS and to evaluate its risk factors. A prospective study was conducted on all children (age 6 months to 6 years) referred with initial FS to the Shahid Sadoughi Hospital, Yazd, Iran, between August 2004 and March 2006, who were followed up for at least 15 months for the occurrence of subsequent afebrile seizures. 161 boys and 120 girls (mean age 2.12 ± 1.33 years) were followed up for 34.1 ± 7.8 months. 87 (31%) patients had complex FS and 19 (6.7%) patients had subsequent afebrile seizure, with a mean occurrence time of 10.6 ± 6.4 months. Univariate analysis using chi-square test showed that initial FS within one hour of developing fever (p = 0.0001), neurodevelopmental delay (p = 0.0001), family history of epilepsy (p = 0.0001), recurrent FS (p = 0.003) and focal FS (p = 0.04) were risk factors for subsequent afebrile seizure. On multivariate analysis, neurodevelopmental delay (odds ratio [OR] 2.6, 95% confidence interval [CI] 2.3-3.4), initial FS within one hour of developing fever (OR 1.7, 95% CI 1.2-2.1) and family history of epilepsy (OR 1.5, 95% CI 1.1-1.9) were significant factors. Special attention should be paid to children with FS during history-taking and developmental assessments to identify high-risk patients and those who might need prophylactic anticonvulsants.

5p14 deletion associated with microcephaly and seizures

PubMed Central

Johnson, E.; Marinescu, R; Punnett, H.; Tenenholz, B.; Overhauser, J.

2000-01-01

We report on a father and son who have an interstitial deletion of 5p14. The father is clinically and mentally normal while the son has significant clinical involvement including microcephaly, seizures, and global developmental delay. The extent of the 5p14 deletion was determined using fluorescence in situ hybridisation (FISH). The deletion in this present family is smaller than a deletion previously described in a multigenerational family that lacks any clinical phenotype. This report shows that a 5p14 deletion does not always lead to a normal phenotype.


Keywords: interstitial deletion; chromosome 5; fluorescence in situ hybridisation; cri du chat syndrome PMID:10662813

Seizure disorders and developmental disorders: impact on life of affected families-a structured interview.

PubMed

Spindler, Ulrike Petra; Hotopp, Lena Charlott; Bach, Vivien Angela; Hornemann, Frauke; Syrbe, Steffen; Andreas, Anna; Merkenschlager, Andreas; Kiess, Wieland; Bernhard, Matthias Karl; Bertsche, Thilo; Neininger, Martina Patrizia; Bertsche, Astrid

2017-08-01

Seizure disorder and developmental disorder are two of the most common chronic disorders in childhood. Data on perceived parental burden and specific effects on daily life is scarce. We performed a structured interview, consecutively talking to all parents of pediatric outpatients of our university hospital diagnosed with seizure or developmental disorder. Three hundred seven parents (of 317 affected children: 53 with seizure disorder, 44 with specific developmental disorder, 35 with learning disorder, 71 with intellectual disability, 15 with seizure + specific developmental disorder, 23 with seizure + learning disorder, 76 with seizure disorder + intellectual disability) were interviewed. Parents of children with both seizure disorder and intellectual disability stated the highest constraints in daily life, regarding friends, hobbies, emotional pressure, occupation, partnership, habitation, and financial burden. Due to diagnosis of seizure or developmental disorder, 155/307 (51%) parents reduced their working hours/stopped working, 62/307 (20%) changed their habitation, and 46/307 (15%) broke up. As judged by parents, 148/317 (47%) children are being discriminated against, even own family/friends and educators are held responsible. Parents perceive changes in their daily life and discrimination of their children due to their children's seizure and developmental disorders. An intellectual disability combined with seizure disorder caused the highest constraint. What is Known: • Seizure and/or developmental disorders of children may adversely influence quality of life for affected parents. • Caring for a child with special health care needs can take complete attention and own parental needs may therefore be difficult to meet. What is New: • Two out of three parents stated changes of their daily life such as quitting work, change of habitation, or breakup of partnership due to their child's diagnosis. • As judged by the parents, one in two children with developmental disorder of any kind is being discriminated against, even teachers and own family are held responsible.

Predictors of intractable childhood epilepsy.

PubMed

Seker Yilmaz, Berna; Okuyaz, Cetin; Komur, Mustafa

2013-01-01

Our study sought to identify early predictive factors of medically intractable childhood epilepsy. A cohort of epileptic children from the city of Mersin was retrospectively investigated. All patients received care from the same Department of Pediatric Neurology. The epileptic cohort was divided into a drug-responsive epilepsy group and an intractable epilepsy group. Intractable epilepsy is defined as continued seizures in children despite adequate therapy with two or more antiepileptic drugs for more than 18 months. Strong univariate association was observed between intractability and several factors: age of onset, high initial seizure frequency, symptomatic etiology, mixed seizure types, previous history of status epilepticus, febrile and neonatal seizures, mental and motor developmental delay, multiple seizures in 1 day, electroencephalogram abnormalities, magnetic resonance imaging findings, and specific epileptic syndromes. Logistic regression analysis revealed that a previous history of epilepticus status, abnormal electroencephalogram results, and multiple seizures in 1 day comprise independent predictors of medically intractable childhood epilepsy. We suggest that medical intractability in childhood epilepsy can be predicted by monitoring these factors. Along with early prediction, alternative therapies may be designed to provide patients better seizure control and quality of life. Copyright © 2013 Elsevier Inc. All rights reserved.

Autosomal dominant SCN8A mutation with an unusually mild phenotype.

PubMed

Anand, G; Collett-White, F; Orsini, A; Thomas, S; Jayapal, S; Trump, N; Zaiwalla, Z; Jayawant, S

2016-09-01

Mutations in SCN8A, coding for the voltage-gated sodium channel Nav 1.6, have been described in relation to infantile onset epilepsy with developmental delay and cognitive impairment, in particular early onset epileptic encephalopathy (EIEE) type 13. Here we report an infant and his father with early onset focal epileptic seizures but without cognitive or neurological impairment in whom next generation sequence analysis identified a heterozygous mutation (c.5630A > G, p. (Asn1877Ser)) in the SCN8A gene. This mutation, confirmed by Sanger sequence analysis, affects a highly conserved amino acid and in silico tools predicts that it may be pathogenic. The reported infant has a normal developmental profile at 16-month follow-up. His father also had normal development and has no cognitive impairment at 42 years. This is the second known SCN8A mutation associated with a phenotype of benign familial infantile epilepsy. Good seizure control was achieved in our patients with sodium channel blockers. Based on our proband and a recently described group of families with benign familial infantile epilepsy and SCN8A variant we suggest expanding testing to patients with infantile epilepsy and no cognitive impairment. In addition, the same SCN8A variant (c.5630A > G, p. (Asn1877Ser)) is also found in patients with epilepsy and developmental delay highlighting the phenotypic variability and the possible role of other protective genetic factors. Copyright © 2016. Published by Elsevier Ltd.

Early-onset seizures due to mosaic exonic deletions of CDKL5 in a male and two females.

PubMed

Bartnik, Magdalena; Derwińska, Katarzyna; Gos, Monika; Obersztyn, Ewa; Kołodziejska, Katarzyna E; Erez, Ayelet; Szpecht-Potocka, Agnieszka; Fang, Ping; Terczyńska, Iwona; Mierzewska, Hanna; Lohr, Naomi J; Bellus, Gary A; Reimschisel, Tyler; Bocian, Ewa; Mazurczak, Tadeusz; Cheung, Sau Wai; Stankiewicz, Paweł

2011-05-01

Mutations in the CDKL5 gene have been associated with an X-linked dominant early infantile epileptic encephalopathy-2. The clinical presentation is usually of severe encephalopathy with refractory seizures and Rett syndrome (RTT)-like phenotype. We attempted to assess the role of mosaic intragenic copy number variation in CDKL5. We have used comparative genomic hybridization with a custom-designed clinical oligonucleotide array targeting exons of selected disease and candidate genes, including CDKL5. We have identified mosaic exonic deletions of CDKL5 in one male and two females with developmental delay and medically intractable seizures. These three mosaic changes represent 60% of all deletions detected in 12,000 patients analyzed by array comparative genomic hybridization and involving the exonic portion of CDKL5. We report the first case of an exonic deletion of CDKL5 in a male and emphasize the importance of underappreciated mosaic exonic copy number variation in patients with early-onset seizures and RTT-like features of both genders.

Association of the missense variant p.Arg203Trp in PACS1 as a cause of intellectual disability and seizures.

PubMed

Stern, D; Cho, M T; Chikarmane, R; Willaert, R; Retterer, K; Kendall, F; Deardorff, M; Hopkins, S; Bedoukian, E; Slavotinek, A; Schrier Vergano, S; Spangler, B; McDonald, M; McConkie-Rosell, A; Burton, B K; Kim, K H; Oundjian, N; Kronn, D; Chandy, N; Baskin, B; Guillen Sacoto, M J; Wentzensen, I M; McLaughlin, H M; McKnight, D; Chung, W K

2017-08-01

Graphical abstract key: ADHD, attention deficit hyperactivity disorder; ASD, atrial septal defect; DD, developmental delay; EEG, electroencephalogram; Ht, height; ID, intellectual disability; OCD, obsessive-compulsive disorder; OFC, open fontanelle; PDA, patent ductus arteriosis; PFO, patent foramen ovale; VSD, ventricular septal defect; Wt, weight. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A PIGN Mutation Responsible for Multiple Congenital Anomalies–Hypotonia–Seizures Syndrome 1 (MCAHS1) in an Israeli–Arab Family

PubMed Central

Khayat, Morad; Tilghman, Joseph Mark; Chervinsky, Ilana; Zalman, Lucia; Chakravarti, Aravinda; Shalev, Stavit A.

2017-01-01

Mutations in the PIGN gene involved in the glycosylphoshatidylinositol (GPI) anchor biosynthesis pathway cause Multiple Congenital Anomalies–Hypotonia–Seizures syndrome 1 (MCAHS1). The syndrome manifests developmental delay, hypotonia, and epilepsy, combined with multiple congenital anomalies. We report on the identification of a homozygous novel c.755A>T (p.D252V) deleterious mutation in a patient with Israeli–Arab origin with MCAHS1. The mutated PIGN caused a significant decrease of the overall GPI-anchored proteins and CD24 expression. Our results, strongly support previously published data, that partial depletion of GPI-anchored proteins is sufficient to cause severe phenotypic expression. PMID:26364997

Multiscale Entropy of Electroencephalogram as a Potential Predictor for the Prognosis of Neonatal Seizures.

PubMed

Lu, Wen-Yu; Chen, Jyun-Yu; Chang, Chi-Feng; Weng, Wen-Chin; Lee, Wang-Tso; Shieh, Jiann-Shing

2015-01-01

Increasing animal studies supported the harmful effects of prolonged or frequent neonatal seizures in developing brain, including increased risk of later epilepsy. Various nonlinear analytic measures had been applied to investigate the change of brain complexity with age. This study focuses on clarifying the relationship between later epilepsy and the changes of electroencephalogram (EEG) complexity in neonatal seizures. EEG signals from 19 channels of the whole brain from 32 neonates below 2 months old were acquired. The neonates were classified into 3 groups: 9 were normal controls, 9 were neonatal seizures without later epilepsy, and 14 were neonatal seizures with later epilepsy. Sample entropy (SamEn), multiscale entropy (MSE) and complexity index (CI) were analyzed. Although there was no significant change in SamEn, the CI values showed significantly decreased over Channels C3, C4, and Cz in patients with neonatal seizures and later epilepsy compared with control group. More multifocal epileptiform discharges in EEG, more abnormal neuroimaging findings, and higher incidence of future developmental delay were noted in the group with later epilepsy. Decreased MSE and CI values in patients with neonatal seizures and later epilepsy may reflect the mixed effects of acute insults, underlying brain immaturity, and prolonged seizures-related injuries. The analysis of MSE and CI can therefore provide a quantifiable and accurate way to decrypt the mystery of neonatal seizures, and could be a promising predictor.

Viscum Album in the Treatment of a Girl With Refractory Childhood Absence Epilepsy.

PubMed

von Schoen-Angerer, Tido; Madeleyn, René; Kienle, Gunver; Kiene, Helmut; Vagedes, Jan

2015-07-01

Viscum album (European mistletoe) extracts have known immunomodulatory effects but little data exist on anticonvulsant activity despite its usefulness having been reported for centuries. A 4½-year-old girl with childhood absence epilepsy and global developmental delay was treated with different antiepileptic drugs and ketogenic diet but failed to become seizure free over a 2-year period. She also received different herbal remedies as part of an integrative medicine approach. Initial improvement occurred on valproate-ethosuximide, a further improvement was seen after adding clobazam to valproate. Final cessation of absence activity occurred after a dose increase of V album. She was still seizure free at the 12-month follow-up. V album appears to have been a necessary adjunct treatment for this child to become seizure free. We call on physicians to report their experiences of V album in epilepsy and suggest further study. © The Author(s) 2014.

Developmental outcomes in Malawian children with retinopathy-positive cerebral malaria.

PubMed

Boivin, Michael J; Gladstone, Melissa J; Vokhiwa, Maclean; Birbeck, Gretchen L; Magen, Jed G; Page, Connie; Semrud-Clikeman, Margaret; Kauye, Felix; Taylor, Terrie E

2011-03-01

To assess children with retinopathy-positive cerebral malaria (CM) for neurocognitive sequelae. Participants were selected from an ongoing exposure-control study. Eighty-three Malawian children averaging 4.4 years of age and diagnosed with retinopathy-positive CM were compared to 95 controls. Each child was classified as delayed or not using age-based norms for the Malawi Developmental Assessment Tool (MDAT) for developmental delay on the total scale and for the domains of gross motor, fine motor, language and social skills. Groups were also compared on the Achenbach Child Behaviour Checklist (CBCL) (1.5-5 years). Children with retinopathy-positive CM were delayed, relative to the comparison group, on MDAT total development (P = 0.028; odds ratio or OR = 2.13), with the greatest effects on language development (P = 0.003; OR = 4.93). The two groups did not differ significantly on the Achenbach CBCL internalizing and externalizing symptoms total scores. Stepwise regression demonstrated that coma duration, seizures while in hospital, platelet count and lactate level on admission were predictive of assessment outcomes for the children with retinopathy-positive CM. Children who suffer retinopathy-positive CM at preschool age are at greater risk of developmental delay, particularly with respect to language development. This confirms previous retrospective study findings with school-age children evaluated years after acute illness. The MDAT and the Achenbach CBCL proved sensitive to clinical indicators of severity of malarial illness. © 2010 Blackwell Publishing Ltd.

Descriptive Analysis of Epileptic Seizures and Problem Behavior in Adults with Developmental Disabilities

ERIC Educational Resources Information Center

Roberts, Celeste; Yoder, Paul J.; Kennedy, Craig H.

2006-01-01

We studied possible relations between seizures and problem behavior in 3 adults with developmental disabilities. Each person was observed for between 56 and 92 days to record occurrences of seizures and problem behavior. Results of our descriptive analysis indicated an association between seizures and problem behavior for each participant. For…

Diagnostic delay in psychogenic seizures and the association with anti-seizure medication trials.

PubMed

Kerr, Wesley T; Janio, Emily A; Le, Justine M; Hori, Jessica M; Patel, Akash B; Gallardo, Norma L; Bauirjan, Janar; Chau, Andrea M; D'Ambrosio, Shannon R; Cho, Andrew Y; Engel, Jerome; Cohen, Mark S; Stern, John M

2016-08-01

The average delay from first seizure to diagnosis of psychogenic non-epileptic seizures (PNES) is over 7 years. The reason for this delay is not well understood. We hypothesized that a perceived decrease in seizure frequency after starting an anti-seizure medication (ASM) may contribute to longer delays, but the frequency of such a response has not been well established. Time from onset to diagnosis, medication history and associated seizure frequency was acquired from the medical records of 297 consecutive patients with PNES diagnosed using video-electroencephalographic monitoring. Exponential regression was used to model the effect of medication trials and response on diagnostic delay. Mean diagnostic delay was 8.4 years (min 1 day, max 52 years). The robust average diagnostic delay was 2.8 years (95% CI: 2.2-3.5 years) based on an exponential model as 10 to the mean of log10 delay. Each ASM trial increased the robust average delay exponentially by at least one third of a year (Wald t=3.6, p=0.004). Response to ASM trials did not significantly change diagnostic delay (Wald t=-0.9, p=0.38). Although a response to ASMs was observed commonly in these patients with PNES, the presence of a response was not associated with longer time until definitive diagnosis. Instead, the number of ASMs tried was associated with a longer delay until diagnosis, suggesting that ASM trials were continued despite lack of response. These data support the guideline that patients with seizures should be referred to epilepsy care centers after failure of two medication trials. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Developmental outcome after a single episode of status epilepticus.

PubMed

Roy, Hélène; Lippé, Sarah; Lussier, Francine; Sauerwein, Hannelore Catherine; Lortie, Anne; Lacroix, Jacques; Lassonde, Maryse

2011-08-01

Consequences of status epilepticus (SE) on psychomotor development and the specific impact of the convulsive event on emerging executive functions remain controversial. Infants treated for a single episode of SE, those treated for a single febrile seizure, and healthy infants were tested with respect to motor development, language, personal, and social skills and self-regulation. The children were divided into two age groups to investigate the impact of the convulsive event at different windows of brain maturation. We found that infants who had had SE were inferior to healthy controls on the development scales. Age differentiated SE impact on visuomotor development versus sociolinguistic development. Children who had been treated for SE had significantly more difficulties delaying a response to an attractive stimulus in one of the long-delay conditions. A single episode of SE can interfere with psychomotor and cognitive development in children without previous developmental delay, and it seems that the functions that are emerging at the time of insult are most vulnerable. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Delayed seizures after intracerebral haemorrhage

PubMed Central

Rattani, Abbas; Anderson, Christopher D.; Ayres, Alison M.; Gurol, Edip M.; Greenberg, Steven M.; Rosand, Jonathan; Viswanathan, Anand

2016-01-01

Late seizures after intracerebral haemorrhage occur after the initial acute haemorrhagic insult subsides, and represent one of its most feared long-term sequelae. Both susceptibility to late seizures and their functional impact remain poorly characterized. We sought to: (i) compare patients with new-onset late seizures (i.e. delayed seizures), with those who experienced a recurrent late seizure following an immediately post-haemorrhagic seizure; and (ii) investigate the effect of late seizures on long-term functional performance after intracerebral haemorrhage. We performed prospective longitudinal follow-up of consecutive intracerebral haemorrhage survivors presenting to a single tertiary care centre. We tested for association with seizures the following neuroimaging and genetic markers of cerebral small vessel disease: APOE variants ε2/ε4, computer tomography-defined white matter disease, magnetic resonance imaging-defined white matter hyperintensities volume and cerebral microbleeds. Cognitive performance was measured using the Modified Telephone Interview for Cognitive Status, and functional performance using structured questionnaires obtained every 6 months. We performed time-to-event analysis using separate Cox models for risk to develop delayed and recurrent seizures, as well as for functional decline risk (mortality, incident dementia, and loss of functional independence) after intracerebral haemorrhage. A total of 872 survivors of intracerebral haemorrhage were enrolled and followed for a median of 3.9 years. Early seizure developed in 86 patients, 42 of whom went on to experience recurrent seizures. Admission Glasgow Coma Scale, increasing haematoma volume and cortical involvement were associated with recurrent seizure risk (all P < 0.01). Recurrent seizures were not associated with long-term functional outcome (P = 0.67). Delayed seizures occurred in 37 patients, corresponding to an estimated incidence of 0.8% per year (95% confidence interval 0.5–1.2%). Factors associated with delayed seizures included cortical involvement on index haemorrhage (hazard ratio 1.63, P = 0.036), pre-haemorrhage dementia (hazard ratio 1.36, P = 0.044), history of multiple prior lobar haemorrhages (hazard ratio 2.50, P = 0.038), exclusively lobar microbleeds (hazard ratio 2.22, P = 0.008) and presence of ≥ 1 APOE ε4 copies (hazard ratio 1.95, P = 0.020). Delayed seizures were associated with worse long-term functional outcome (hazard ratio 1.83, P = 0.005), but the association was removed by adjusting for neuroimaging and genetic markers of cerebral small vessel disease. Delayed seizures after intracerebral haemorrhage are associated with different risk factors, when compared to recurrent seizures. They are also associated with worse functional outcome, but this finding appears to be related to underlying small vessel disease. Further investigations into the connections between small vessel disease and delayed seizures are warranted. PMID:27497491

Historic, clinical, and prognostic features of epileptic encephalopathies caused by CDKL5 mutations.

PubMed

Moseley, Brian D; Dhamija, Radhika; Wirrell, Elaine C; Nickels, Katherine C

2012-02-01

Mutations within the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene are important causes of early-onset epileptic encephalopathies. We sought to determine the historic, clinical, and prognostic features of epilepsy secondary to CDKL5 mutations. We performed retrospective chart reviews of children at our institution with epilepsy and CDKL5 mutations. Six children were identified. One manifested a deletion in exons 10-15 of the CDKL5 gene, another manifested a single base-pair duplication in exon 3, and the rest manifested base-pair exchanges. The mean age of seizure onset was 1.8 months (range, 1-3 months). Although the majority (4/6, 67%) presented with partial-onset seizures, all children developed infantile spasms. All children demonstrated developmental delay and visual impairment. Although such mutations are X-linked, two children were boys. They did not present with more severe phenotypes than their female counterparts. Despite trials of antiepileptic drugs (mean, 5; range, 3-7), steroids/adrenocorticotropic hormone (4/6; 67%), and the ketogenic diet (6/6; 100%), all children manifested refractory seizures at last follow-up. Although no treatment eliminated seizures, topiramate, vigabatrin, and the ketogenic diet were most helpful at reducing seizure frequency. Copyright © 2012 Elsevier Inc. All rights reserved.

Usefulness of ketogenic diet in a girl with migrating partial seizures in infancy.

PubMed

Mori, Tatsuo; Imai, Katsumi; Oboshi, Taikan; Fujiwara, Yuh; Takeshita, Saoko; Saitsu, Hirotomo; Matsumoto, Naomichi; Takahashi, Yukitoshi; Inoue, Yushi

2016-06-01

Migrating partial seizures in infancy (MPSI) are an age-specific epilepsy syndrome characterized by migrating focal seizures, which are intractable to various antiepileptic drugs and cause severe developmental delay. We report a case of MPSI with heterozygous missense mutation in KCNT1, which was successfully managed by ketogenic diet. At age 2months, the patient developed epilepsy initially manifesting focal seizures with eye deviation and apnea, then evolving to secondarily generalized clonic convulsion. Various antiepileptic drugs including phenytoin, valproic acid, zonisamide, clobazam, levetiracetam, vitamin B6, and carbamazepine were not effective, but high-dose phenobarbital allowed discontinuation of midazolam infusion. Ictal scalp electroencephalogram showed migrating focal seizures. MPSI was suspected and she was transferred to our hospital for further treatment. Potassium bromide (KBr) was partially effective, but the effect was transient. High-dose KBr caused severe adverse effects such as over-sedation and hypercapnia, with no further effects on the seizures. At age 9months, we started a ketogenic diet, which improved seizure frequency and severity without obvious adverse effects, allowing her to be discharged from hospital. Ketogenic diet should be tried in patients with MPSI unresponsive to antiepileptic drugs. In MPSI, the difference in treatment response in patients with and those without KCNT1 mutation remains unknown. Accumulation of case reports would contribute to establish effective treatment options for MPSI. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Microcephalic primordial dwarfism in an Emirati patient with PNKP mutation.

PubMed

Nair, Pratibha; Hamzeh, Abdul Rezzak; Mohamed, Madiha; Saif, Fatima; Tawfiq, Nafisa; El Halik, Majdi; Al-Ali, Mahmoud Taleb; Bastaki, Fatma

2016-08-01

Microcephaly is a rare neurological condition, both in isolation and when it occurs as part of a syndrome. One of the syndromic forms of microcephaly is microcephaly, seizures and developmental delay (MCSZ) (OMIM #613402), a rare autosomal recessive neurodevelopmental disorder with a range of phenotypic severity, and known to be caused by mutations in the polynucleotide kinase 3' phosphatase (PNKP) gene. The PNK protein is a key enzyme involved in the repair of single and double stranded DNA breaks, a process which is particularly important in the nervous system. We describe an Emirati patient who presented with microcephaly, short stature, uncontrollable tonic-clonic seizures, facial dysmorphism, and developmental delay, while at the same time showing evidence of brain atrophy and agenesis of the corpus callosum. We used whole exome sequencing to identify homozygosity for a missense c.1385G > C (p.Arg462Pro) mutation in PNKP in the patient and heterozygosity for this mutation in her consanguineous parents. The Arg 462 residue forms a part of the lid subdomain helix of the P-loop Kinase domain. Although our patient's phenotype resembled that of MCSZ, the short stature and evidence of brain atrophy distinguished it from other classic cases of the condition. The report raises the question of whether to consider this case as an atypical variant of MCSZ or as a novel form of microcephalic primordial dwarfism. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effect of vaccinations on seizure risk and disease course in Dravet syndrome.

PubMed

Verbeek, Nienke E; van der Maas, Nicoline A T; Sonsma, Anja C M; Ippel, Elly; Vermeer-de Bondt, Patricia E; Hagebeuk, Eveline; Jansen, Floor E; Geesink, Huibert H; Braun, Kees P; de Louw, Anton; Augustijn, Paul B; Neuteboom, Rinze F; Schieving, Jolanda H; Stroink, Hans; Vermeulen, R Jeroen; Nicolai, Joost; Brouwer, Oebele F; van Kempen, Marjan; de Kovel, Carolien G F; Kemmeren, Jeanet M; Koeleman, Bobby P C; Knoers, Nine V; Lindhout, Dick; Gunning, W Boudewijn; Brilstra, Eva H

2015-08-18

To study the effect of vaccination-associated seizure onset on disease course and estimate the risk of subsequent seizures after infant pertussis combination and measles, mumps, and rubella (MMR) vaccinations in Dravet syndrome (DS). We retrospectively analyzed data from hospital medical files, child health clinics, and the vaccination register for children with DS and pathogenic SCN1A mutations. Seizures within 24 hours after infant whole-cell, acellular, or nonpertussis combination vaccination or within 5 to 12 days after MMR vaccination were defined as "vaccination-associated." Risks of vaccination-associated seizures for the different vaccines were analyzed in univariable and in multivariable logistic regression for pertussis combination vaccines and by a self-controlled case series analysis using parental seizure registries for MMR vaccines. Disease courses of children with and without vaccination-associated seizure onset were compared. Children who had DS (n = 77) with and without vaccination-associated seizure onset (21% and 79%, respectively) differed in age at first seizure (median 3.7 vs 6.1 months, p < 0.001) but not in age at first nonvaccination-associated seizure, age at first report of developmental delay, or cognitive outcome. The risk of subsequent vaccination-associated seizures was significantly lower for acellular pertussis (9%; odds ratio 0.18, 95% confidence interval [CI] 0.05-0.71) and nonpertussis (8%; odds ratio 0.11, 95% CI 0.02-0.59) than whole-cell pertussis (37%; reference) vaccines. Self-controlled case series analysis showed an increased incidence rate ratio of seizures of 2.3 (95% CI 1.5-3.4) within the risk period of 5 to 12 days following MMR vaccination. Our results suggest that vaccination-associated earlier seizure onset does not alter disease course in DS, while the risk of subsequent vaccination-associated seizures is probably vaccine-specific. © 2015 American Academy of Neurology.

Awake craniotomy in a developmentally delayed blind man with cognitive deficits.

PubMed

Burbridge, Mark; Raazi, Mateen

2013-04-01

To describe the complex perioperative considerations and anesthetic management of a cognitively delayed blind adult male who underwent awake craniotomy to remove a left anterior temporal lobe epileptic focus. A 28-yr-old left-handed blind cognitively delayed man was scheduled for awake craniotomy to resect a left anterior temporal lobe epileptic focus due to intractable epilepsy despite multiple medications. His medical history was also significant for retinopathy of prematurity that rendered him legally blind in both eyes and an intracerebral hemorrhage shortly after birth that resulted in a chronic brain injury and developmental delay. His cognitive capacity was comparable with that of an eight year old. Since patient cooperation was the primary concern during the awake electrocorticography phase of surgery, careful assessment of the patient's ability to tolerate the procedure was undertaken. There was extensive planning between surgeons and anesthesiologists, and a patient-specific pharmacological strategy was devised to facilitate surgery. The operation proceeded without complication, the patient has remained seizure-free since the procedure, and his quality of life has improved dramatically. This case shows that careful patient assessment, effective interdisciplinary communication, and a carefully tailored anesthetic strategy can facilitate an awake craniotomy in a potentially uncooperative adult patient with diminished mental capacity and sensory deficits.

CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients

PubMed Central

Archer, H L; Evans, J; Edwards, S; Colley, J; Newbury‐Ecob, R; O'Callaghan, F; Huyton, M; O'Regan, M; Tolmie, J; Sampson, J; Clarke, A; Osborne, J

2006-01-01

Objective To determine the frequency of mutations in CDKL5 in both male and female patients with infantile spasms or early onset epilepsy of unknown cause, and to consider whether the breadth of the reported phenotype would be extended by studying a different patient group. Methods Two groups of patients were investigated for CDKL5 mutations. Group 1 comprised 73 patients (57 female, 16 male) referred to Cardiff for CDKL5 analysis, of whom 49 (42 female, 7 male) had epileptic seizure onset in the first six months of life. Group 2 comprised 26 patients (11 female, 15 male) with infantile spasms previously recruited to a clinical trial, the UK Infantile Spasms Study. Where a likely pathogenic mutation was identified, further clinical data were reviewed. Results Seven likely pathogenic mutations were found among female patients from group 1 with epileptic seizure onset in the first six months of life, accounting for seven of the 42 in this group (17%). No mutations other than the already published mutation were found in female patients from group 2, or in any male patient from either study group. All patients with mutations had early signs of developmental delay and most had made little developmental progress. Further clinical information was available for six patients: autistic features and tactile hypersensitivity were common but only one had suggestive Rett‐like features. All had a severe epileptic seizure disorder, all but one of whom had myoclonic jerks. The EEG showed focal or generalised changes and in those with infantile spasms, hypsarrhythmia. Slow frequencies were seen frequently with a frontal or fronto‐temporal predominance and high amplitudes. Conclusions The spectrum of the epileptic seizure disorder, and associated EEG changes, in those with CDKL5 mutations is broader than previously reported. CDKL5 mutations are a significant cause of infantile spasms and early epileptic seizures in female patients, and of a later intractable seizure disorder, irrespective of whether they have suspected Rett syndrome. Analysis should be considered in these patients in the clinical setting. PMID:16611748

Age dependence of pilocarpine-induced status epilepticus and inhibition of CaM kinase II activity in the rat.

PubMed

Singleton, Michael W; Holbert, William H; Ryan, Matthew L; Lee, Anh Tuyet; Kurz, Jonathan E; Churn, Severn B

2005-04-21

This study was conducted to characterize the post-pubertal developmental aspects on seizure susceptibility and severity as well as calcium/calmodulin protein kinase type II (CaM kinase II) activity in status epilepticus (SE). Thirty- to ninety-day-old rats, in 10-day increments, were studied. This corresponds to a developmental age group that has not received thorough attention. The pilocarpine model of SE was characterized both behaviorally and electrographically. Seven criteria were analyzed for electrographical characterization: seizure severity, SE susceptibility, the average number of discrete seizures, average time until first seizure, average time to SE, average time from first discrete seizure to SE, and death. After 1 h of SE, specific brain regions were isolated for biochemical study. Phosphate incorporation into a CaM kinase II-specific substrate, autocamtide III, was used to determine kinase activity. There was no developmental effect on the average number of discrete seizures, average time until first seizure, average time to SE, average time from first discrete seizure to SE, and death; however, there was a significant effect on SE probability and seizure severity. Once SE was expressed, all animals showed a decrease in both cortical and hippocampal CaM kinase II activities. Conversely, seizure activity in the absence of SE did not result in a decrease in CaM kinase II activity. The data suggest that there is a gradual age-dependent modulation of SE susceptibility and seizure severity within the developmental stages studied. Additionally, once status epilepticus is observed at any age, there is a corresponding SE-induced inhibition of CaM kinase II.

The incidence of unprovoked seizures and occurrence of neurodevelopmental comorbidities in children at the time of their first epileptic seizure and during the subsequent six months.

PubMed

Åndell, Eva; Tomson, Torbjörn; Carlsson, Sofia; Hellebro, Eva; Andersson, Tomas; Adelöw, Cecilia; Åmark, Per

2015-07-01

To evaluate the incidence of unprovoked seizures in children and the prevalence of related neurodevelopmental comorbidities at the time of the presumed first seizure and six months thereafter. The medical records of all children (0-18 years of age) seeking medical attention as the result of a first unprovoked seizure between September 1, 2001 and December 31, 2006, and registered in the population-based Stockholm Incidence Registry of Epilepsy (SIRE) were reviewed. Neurodevelopmental comorbidities were evaluated on the basis of the medical records from this first visit and from other healthcare during the following six months. The incidence of unprovoked seizures was between 30 and 204/100,000 person years (n=766) in the different age groups. It was highest among the youngest children and lowest among the 18-year-olds with small gender differences. The most common neurodevelopment comorbidities were developmental delay (22%, CI: 19-25%), speech/language and learning difficulties (23%, CI: 20-26%) and intellectual disability (16%, CI: 13-18%). The types of neurodevelopmental comorbidity varied by age at the time of seizure onset, with cerebral palsy being more common among the 0-5-year-olds, attention deficits among the 6-16-year-olds, and autism and psychiatric diagnosis among the older children. An associated neurodevelopmental comorbidity was more common among those experiencing recurrent than single seizures during follow-up six months from the index seizure (42% versus 66%). In 68% (CI: 64-71%) of the children there was no known or suspected neurodevelopmental comorbidity. The incidence of unprovoked, non-febrile seizures among 0-18-year-olds included in the SIRE was 67/100,000 person-years. Neurodevelopmental comorbidities were common already at the time of onset of the seizure disorder, indicating that neither seizure treatment nor seizures were the underlying cause of other neurodevelopmental symptoms in these patients during the period studied. Copyright © 2015 Elsevier B.V. All rights reserved.

Anesthetic considerations in Leigh disease: Case report and literature review.

PubMed

Terkawi, Abdullah Sulieman; Wani, Tariq M; Al-Shuaibi, Khalid M; Tobias, Joseph D

2012-04-01

Leigh disease is an extremely rare disorder, characterized by a progressive neurodegenerative course, with subacute necrotizing encephalomyelopathy. It usually presents in infancy with developmental delay, seizures, dysarthria, and ataxia. These patients may also develop episodes of lactic acidosis that usually lead to respiratory failure and death. Due to the rarity of the condition, the most appropriate anesthetic plan remains unclear. We present a patient with Leigh disease, who required general anesthesia. The pathogenesis of the disease is discussed and previous reports of perioperative care from the literature are reviewed.

Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis.

PubMed

Veroniki, Areti Angeliki; Rios, Patricia; Cogo, Elise; Straus, Sharon E; Finkelstein, Yaron; Kealey, Ryan; Reynen, Emily; Soobiah, Charlene; Thavorn, Kednapa; Hutton, Brian; Hemmelgarn, Brenda R; Yazdi, Fatemeh; D'Souza, Jennifer; MacDonald, Heather; Tricco, Andrea C

2017-07-20

Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding. Systematic review and Bayesian random-effects network meta-analysis (NMA). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched until 27 April 2017. Screening, data abstraction and quality appraisal were completed in duplicate by independent reviewers. 29 cohort studies including 5100 infants/children. Monotherapy and polytherapy AEDs including first-generation (carbamazepine, clobazam, clonazepam, ethosuximide, phenobarbital, phenytoin, primidone, valproate) and newer-generation (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin) AEDs. Epileptic women who did not receive AEDs during pregnancy or breast feeding served as the control group. Cognitive developmental delay and autism/dyspraxia were primary outcomes. Attention-deficit hyperactivity disorder, language delay, neonatal seizures, psychomotor developmental delay and social impairment were secondary outcomes. The NMA on cognitive developmental delay (11 cohort studies, 933 children, 18 treatments) suggested that among all AEDs only valproate was statistically significantly associated with more children experiencing cognitive developmental delay compared with control (OR=7.40, 95% credible interval (CrI) 3.00 to 18.46). The NMA on autism (5 cohort studies, 2551 children, 12 treatments) suggested that oxcarbazepine (OR 13.51, CrI 1.28 to 221.40), valproate (OR 17.29, 95% CrI 2.40 to 217.60), lamotrigine (OR 8.88, CrI 1.28 to 112.00) and lamotrigine+valproate (OR 132.70, CrI 7.41 to 3851.00) were associated with significantly greater odds of developing autism compared with control. The NMA on psychomotor developmental delay (11 cohort studies, 1145 children, 18 treatments) found that valproate (OR 4.16, CrI 2.04 to 8.75) and carbamazepine+phenobarbital+valproate (OR 19.12, CrI 1.49 to 337.50) were associated with significantly greater odds of psychomotor delay compared with control. Valproate alone or combined with another AED is associated with the greatest odds of adverse neurodevelopmental outcomes compared with control. Oxcarbazepine and lamotrigine were associated with increased occurrence of autism. Counselling is advised for women considering pregnancy to tailor the safest regimen. PROSPERO database (CRD42014008925). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis

PubMed Central

Veroniki, Areti Angeliki; Rios, Patricia; Cogo, Elise; Straus, Sharon E; Finkelstein, Yaron; Kealey, Ryan; Reynen, Emily; Soobiah, Charlene; Thavorn, Kednapa; Hutton, Brian; Hemmelgarn, Brenda R; Yazdi, Fatemeh; D'Souza, Jennifer; MacDonald, Heather; Tricco, Andrea C

2017-01-01

Objectives Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding. Design and setting Systematic review and Bayesian random-effects network meta-analysis (NMA). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched until 27 April 2017. Screening, data abstraction and quality appraisal were completed in duplicate by independent reviewers. Participants 29 cohort studies including 5100 infants/children. Interventions Monotherapy and polytherapy AEDs including first-generation (carbamazepine, clobazam, clonazepam, ethosuximide, phenobarbital, phenytoin, primidone, valproate) and newer-generation (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin) AEDs. Epileptic women who did not receive AEDs during pregnancy or breast feeding served as the control group. Primary and secondary outcome measures Cognitive developmental delay and autism/dyspraxia were primary outcomes. Attention-deficit hyperactivity disorder, language delay, neonatal seizures, psychomotor developmental delay and social impairment were secondary outcomes. Results The NMA on cognitive developmental delay (11 cohort studies, 933 children, 18 treatments) suggested that among all AEDs only valproate was statistically significantly associated with more children experiencing cognitive developmental delay compared with control (OR=7.40, 95% credible interval (CrI) 3.00 to 18.46). The NMA on autism (5 cohort studies, 2551 children, 12 treatments) suggested that oxcarbazepine (OR 13.51, CrI 1.28 to 221.40), valproate (OR 17.29, 95% CrI 2.40 to 217.60), lamotrigine (OR 8.88, CrI 1.28 to 112.00) and lamotrigine+valproate (OR 132.70, CrI 7.41 to 3851.00) were associated with significantly greater odds of developing autism compared with control. The NMA on psychomotor developmental delay (11 cohort studies, 1145 children, 18 treatments) found that valproate (OR 4.16, CrI 2.04 to 8.75) and carbamazepine+phenobarbital+valproate (OR 19.12, CrI 1.49 to 337.50) were associated with significantly greater odds of psychomotor delay compared with control. Conclusions Valproate alone or combined with another AED is associated with the greatest odds of adverse neurodevelopmental outcomes compared with control. Oxcarbazepine and lamotrigine were associated with increased occurrence of autism. Counselling is advised for women considering pregnancy to tailor the safest regimen. Trial registration number PROSPERO database (CRD42014008925). PMID:28729328

Evaluation of ADD392124 for the Delayed Treatment of Nerve Agent-Induced Status Epilepticus Seizures

DTIC Science & Technology

2011-09-01

Induced Status Epilepticus Seizures John H. McDonough Kerry E. Van Shura Megan E. Lyman Claire G. Eisner Amelia Mazza Robert K. Kan Tsung...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Evaluation of ADD392124 for the delayed treatment of nerve agent-induced status epilepticus seizures 5b... status epilepticus seizures. We evaluated the ability of ADD392124 to control seizures induced by the nerve agent soman. Rats were exposed to a

A girl with early-onset epileptic encephalopathy associated with microdeletion involving CDKL5.

PubMed

Saitsu, Hirotomo; Osaka, Hitoshi; Nishiyama, Kiyomi; Tsurusaki, Yoshinori; Doi, Hiroshi; Miyake, Noriko; Matsumoto, Naomichi

2012-05-01

Recent studies have shown that aberrations of CDKL5 in female patients cause early-onset intractable seizures, severe developmental delay or regression, and Rett syndrome-like features. We report on a Japanese girl with early-onset epileptic encephalopathy, hypotonia, developmental regression, and Rett syndrome-like features. The patient showed generalized tonic seizures, and later, massive myoclonus induced by phone and light stimuli. Brain magnetic resonance imaging showed no structural brain anomalies but cerebral atrophy. Electroencephalogram showed frontal dominant diffuse poly spikes and waves. Through copy number analysis by genomic microarray, we found a microdeletion at Xp22.13. A de novo 137-kb deletion, involving exons 5-21 of CDKL5, RS1, and part of PPEF1 gene, was confirmed by quantitative PCR and breakpoint specific PCR analyses. Our report suggests that the clinical features associated with CDKL5 deletions could be implicated in Japanese patients, and that genetic testing of CDKL5, including both sequencing and deletion analyses, should be considered in girls with early-onset epileptic encephalopathy and RTT-like features. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

[A case of non-photosensitive, self-induced epileptic seizures with pacygyria].

PubMed

Nagai, H; Shikata, A; Sato, N; Takeuchi, Y; Sawada, T

1998-09-01

We report an 11-year-old boy with a non-photosensitive epileptic self-induced seizures, pacygyria and familial ataxia. His grandmother and aunts had dysarthria, and his mother had developed progressive ataxia and myoclonus since 40 years old. His older sister had ataxia, mental retardation and epilepsy. As for the boy, motor developmental delay with muscle hypertonicity of left extremities was recognized at the age of 5 months. Mental retardation and ataxia was recognized at the age of 3 years and slight mental regression is recognized at the age of 11 years. No special findings were detected in an examination of his blood and cerebrospinal fluid, including amino acids, lysosomal enzymes activity and genetic analysis for dentatorubralpallidoluysian atrophy. Brain magnetic resonance imaging revealed pachygyria of the right cerebral cortecies. At the age of two, he began to induce seizures with impairment of consciousness in himself by waving his right hand over his face which was directed toward a source of bright light. At the age of seven, he developed spontaneous seizures with impairment of consciousness. An EEG showed frequent spikes in the occipital areas, on the right and left sides occurring either independently or synchronously. Intermittent photic stimulation and pattern stimulation did not induce a paroxysmal discharge in EEG. Ictal EEG suggested that the origin of the seizures was the occipital lobe. Treatment with valporate and zonisamide was effective in reducing the seizures. The findings of our case imply the pathogenesis of self-induced seizures and the relationship between PME and neuronal migration disorders.

Amelioration of intractable epilepsy by adjunct vagus nerve stimulation therapy in a girl with a CDKL5 mutation.

PubMed

Baba, Shimpei; Sugawara, Yuji; Moriyama, Kengo; Inaji, Motoki; Maehara, Taketoshi; Yamamoto, Toshiyuki; Morio, Tomohiro

2017-04-01

We report the case of on an 8-year-old girl with a cyclin-dependent kinase-like 5 mutation and who underwent vagus nerve stimulation (VNS) therapy for 2years. She had developed epilepsy at the age of 6months and had severe developmental delays. Initially, she had tonic and tonic-clonic seizures; however, around the age of 5years, she also developed epileptic spasms. These seizures were never completely controlled by conventional medical treatments. At the age of 7, after VNS initiation, her seizure frequency markedly reduced, and abnormal electrical activities on her electroencephalography tests strikingly decreased. Moreover, using questionnaires, we confirmed an improvement in her quality of life in the fields of alertness and activity. Although the efficacy of VNS therapy for patients with intractable epilepsy associated with a genetic anomaly has not been fully established, adjunctive VNS therapy may widen the scope of treatment choices available to these patients. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Transient dysautonomia in an acute phase of encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Ichimiya, Yuko; Kaku, Noriyuki; Sakai, Yasunari; Yamashita, Fumiya; Matsuoka, Wakato; Muraoka, Mamoru; Akamine, Satoshi; Mizuguchi, Soichi; Torio, Michiko; Motomura, Yoshitomo; Hirata, Yuichiro; Ishizaki, Yoshito; Sanefuji, Masafumi; Torisu, Hiroyuki; Takada, Hidetoshi; Maehara, Yoshihiko; Ohga, Shouichi

2017-08-01

Paroxysmal sympathetic hyperactivity (PSH) is a dysautonomic condition that is associated with various types of acquired brain injuries. Traumatic brain lesions have been documented as the leading cause of PSH. However, detailed clinical features of pediatric PSH caused by intrinsic brain lesions remain to be elusive. We present a 3-year-old boy, who had been diagnosed as having cerebral palsy, developmental delay and epilepsy after perinatal hypoxia-induced brain injury. He developed status epilepticus with fever on the third day of respiratory infection. Whereas the seizure was terminated by systemic infusion of midazolam, consciousness remained disturbed for the next 48h. Serial magnetic resonance imaging studies revealed that acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) evolved on 3days after the seizure. Therapeutic hypothermia was immediately introduced, however, the brain lesion extended to the whole subcortical white matters on day 8. The intermittent bilateral dilation of pupils with increased blood pressure and tachycardia were observed until day 12. Real-time monitoring of electroencephalograms ruled out the recurrent attacks of seizures. The abnormal signs of autonomic nervous system gradually ceased and never relapsed after recovery from the hypothermia. PSH or a transient condition of dysautonomia may emerge and persist during the acute phase of AESD. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

A homozygous loss-of-function CAMK2A mutation causes growth delay, frequent seizures and severe intellectual disability.

PubMed

Chia, Poh Hui; Zhong, Franklin Lei; Niwa, Shinsuke; Bonnard, Carine; Utami, Kagistia Hana; Zeng, Ruizhu; Lee, Hane; Eskin, Ascia; Nelson, Stanley F; Xie, William H; Al-Tawalbeh, Samah; El-Khateeb, Mohammad; Shboul, Mohammad; Pouladi, Mahmoud A; Al-Raqad, Mohammed; Reversade, Bruno

2018-05-22

Calcium/calmodulin-dependent protein kinase II (CAMK2) plays fundamental roles in synaptic plasticity that underlies learning and memory. Here, we describe a new recessive neurodevelopmental syndrome with global developmental delay, seizures and intellectual disability. Using linkage analysis and exome sequencing, we found that this disease maps to chromosome 5q31.1-q34 and is caused by a biallelic germline mutation in CAMK2A . The missense mutation, p.His477Tyr is located in the CAMK2A association domain that is critical for its function and localization. Biochemically, the p.His477Tyr mutant is defective in self-oligomerization and unable to assemble into the multimeric holoenzyme. In vivo , CAMK2A H477Y failed to rescue neuronal defects in C. elegans lacking unc-43 , the ortholog of human CAMK2A. In vitro , neurons derived from patient iPSCs displayed profound synaptic defects. Together, our data demonstrate that a recessive germline mutation in CAMK2A leads to neurodevelopmental defects in humans and suggest that dysfunctional CAMK2 paralogs may contribute to other neurological disorders. © 2018, Chia et al.

Refinement of the deletion in 8q22.2-q22.3: the minimum deletion size at 8q22.3 related to intellectual disability and epilepsy.

PubMed

Kuroda, Yukiko; Ohashi, Ikuko; Saito, Toshiyuki; Nagai, Jun-ichi; Ida, Kazumi; Naruto, Takuya; Iai, Mizue; Kurosawa, Kenji

2014-08-01

Kuechler et al. [2011] reported five patients with interstitial deletions in 8q22.2-q22.3 who had intellectual disability, epilepsy, and dysmorphic features. We report on a new patient with the smallest overlapping de novo deletion in 8q22.3 and refined the phenotype. The proposita was an 8-year-old girl, who developed seizures at 10 months, and her epileptic seizure became severe and difficult to control with antiepileptic drugs. She also exhibited developmental delay and walked alone at 24 months. She was referred to us for evaluation for developmental delay and epilepsy at the age of 8 years. She had intellectual disability (IQ 37 at 7 years) and autistic behavior, and spoke two word sentences at 8 years. She had mild dysmorphic features, including telecanthus and thick vermilion of the lips. Array comparative genomic hybridization detected a 1.36 Mb deletion in 8q22.3 that encompassed RRM2B and NCALD, which encode the small subunit of p53-inducible ribonucleotide reductase and neurocalcin delta in the neuronal calcium sensor family of calcium-binding proteins, respectively. The minimum overlapping region between the present and previously reported patients is considered to be a critical region for the phenotype of the deletion in 8q22.3. We suggest that the deletion in 8q22.3 may represent a clinically recognizable condition, which is characterized by intellectual disability and epilepsy. © 2014 Wiley Periodicals, Inc.

Mutations in the Na+/Citrate Cotransporter NaCT (SLC13A5) in Pediatric Patients with Epilepsy and Developmental Delay

PubMed Central

Klotz, Jenna; Porter, Brenda E; Colas, Claire; Schlessinger, Avner; Pajor, Ana M

2016-01-01

Mutations in the SLC13A5 gene that codes for the Na+/citrate cotransporter, NaCT, are associated with early onset epilepsy, developmental delay and tooth dysplasia in children. In this study, we identify additional SLC13A5 mutations in nine epilepsy patients from six families. To better characterize the syndrome, families with affected children answered questions about the scope of illness and the treatment strategies. Currently, there are no effective treatments, but some antiepileptic drugs targeting the γ-aminobutyric acid system reduce seizure frequency. Acetazolamide, a carbonic anhydrase inhibitor and atypical antiseizure medication, decreases seizures in four patients. In contrast to previous reports, the ketogenic diet and fasting resulted in worsening of symptoms. The effects of the mutations on NaCT transport function and protein expression were examined by transient transfections of COS-7 cells. There was no transport activity from any of the mutant transporters, although some of the mutant transporter proteins were present on the plasma membrane. The structural model of NaCT suggests that these mutations can affect helix packing or substrate binding. We tested various treatments, including chemical chaperones and low temperatures, but none improved transport function in the NaCT mutants. Interestingly, coexpression of NaCT and the mutants results in decreased protein expression and activity of the wild-type transporter, indicating functional interaction. In conclusion, this study has identified additional SLC13A5 mutations in patients with chronic epilepsy starting in the neonatal period, with the mutations producing inactive Na+/citrate transporters. PMID:27261973

Longitudinal study of accelerated long-term forgetting in children with genetic generalized epilepsy: Evidence of ongoing deficits.

PubMed

Grayson-Collins, Jasmin; Gascoigne, Michael B; Barton, Belinda; Webster, Richard; Gill, Deepak; Lah, Suncica

2017-09-15

Accelerated long-term forgetting (ALF) is a recently described memory disorder characterised by adequate recall after short, but not long delays. Currently, the prevailing conceptualisation of ALF is of a seizure related phenomenon. The main aim of this study was to assess whether ALF subsides as epilepsy severity and seizures abate in children with genetic generalized epilepsy (GGE). Eighteen children with GGE were compared over time to 29 healthy controls on a range of cognitive measures. The primary outcome was a modified version of the California Verbal Learning Test for Children with a long delay (seven day) recall component. At approximately two years follow up, ALF was apparent, although epilepsy severity subsided and seizures resolved in many children. This result contrasts with the dominant conceptualisation of ALF being a seizure related phenomenon. Moreover, at follow-up, worse recall at the long delay was related to greater epilepsy severity at baseline and earlier age of seizure onset, but not to being seizure free at follow-up. While at follow-up worse recall at the long delay related to the worse baseline recall at the long delay, this recall did not relate to scores obtained on standardised memory tests at baseline. Our study suggests that ALF may not be seizure related and identifies factors associated with risk of ALF in children with GGE. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inherited Xq13.2-q21.31 duplication in a boy with recurrent seizures and pubertal gynecomastia: Clinical, chromosomal and aCGH characterization.

PubMed

Linhares, Natália D; Valadares, Eugênia R; da Costa, Silvia S; Arantes, Rodrigo R; de Oliveira, Luiz Roberto; Rosenberg, Carla; Vianna-Morgante, Angela M; Svartman, Marta

2016-09-01

We report on a 16-year-old boy with a maternally inherited ~ 18.3 Mb Xq13.2-q21.31 duplication delimited by aCGH. As previously described in patients with similar duplications, his clinical features included intellectual disability, developmental delay, speech delay, generalized hypotonia, infantile feeding difficulties, self-injurious behavior, short stature and endocrine problems. As additional findings, he presented recurrent seizures and pubertal gynecomastia. His mother was phenotypically normal and had completely skewed inactivation of the duplicated X chromosome, as most female carriers of such duplications. Five previously reported patients with partial Xq duplications presented duplication breakpoints similar to those of our patient. One of them, a fetus with multiple congenital abnormalities, had the same cytogenetic duplication breakpoint. Three of the reported patients shared many features with our proband but the other had some clinical features of the Prader-Willi syndrome. It was suggested that ATRX overexpression could be involved in the major clinical features of patients with partial Xq duplications. We propose that this gene could also be involved with the obesity of the patient with the Prader-Willi-like phenotype. Additionally, we suggest that the PCDH11X gene could be a candidate for our patient's recurrent seizures. In males, the Xq13-q21 duplication should be considered in the differential diagnosis of Prader-Willi syndrome, as previously suggested, and neuromuscular diseases, particularly mitochondriopathies.

Williams Syndrome and 15q Duplication: Coincidence versus Association.

PubMed

Khokhar, Aditi; Agarwal, Swashti; Perez-Colon, Sheila

2017-01-01

Williams syndrome is a multisystem disorder caused by contiguous gene deletion in 7q11.23, commonly associated with distinctive facial features, supravalvular aortic stenosis, short stature, idiopathic hypercalcemia, developmental delay, joint laxity, and a friendly personality. The clinical features of 15q11q13 duplication syndrome include autism, mental retardation, ataxia, seizures, developmental delay, and behavioral problems. We report a rare case of a girl with genetically confirmed Williams syndrome and coexisting 15q duplication syndrome. The patient underwent treatment for central precocious puberty and later presented with primary amenorrhea. The karyotype revealed 47,XX,+mar. FISH analysis for the marker chromosome showed partial trisomy/tetrasomy for proximal chromosome 15q (15p13q13). FISH using an ELN -specific probe demonstrated a deletion in the Williams syndrome critical region in 7q11.23. To our knowledge, a coexistence of Williams syndrome and 15q duplication syndrome has not been reported in the literature. Our patient had early pubertal development, which has been described in some patients with Williams syndrome. However, years later after discontinuing gonadotropin-releasing hormone analogue treatment, she developed primary amenorrhea.

Say-Meyer syndrome: additional manifestations in a new patient and phenotypic assessment.

PubMed

Salinas-Torres, Victor M

2015-07-01

In 1981, Say and Meyer described a seemingly X-linked recessive syndrome of trigonocephaly, short stature, and developmental delay. Here, I present a new patient and review eight patients from the literature examining the nature and phenotypic differences. A Mexican 10-year-old boy with Say-Meyer syndrome is described. Additionally, he had C6 vertebral right pedicle agenesis, brachymesophalangy of the fifth fingers, bilateral widening of Sylvian fissure, and white matter amplitude as novel observed findings of the syndrome. This appears to be the first Say-Meyer syndrome patient with extracranial skeletal anomalies. In light of these manifestations, a detailed comparative phenotypic analysis of published patients revealed a heterogeneous syndrome with a significant clinical variability. Moreover, increasing evidence points to a variable expressivity of the same autosomal dominant mutation. Accordingly, it is proposed that Say-Meyer syndrome should be considered in those patients with the combination of trigonocephaly/metopic synostosis, short stature, developmental delay including prenatal and postnatal growth disorders, craniofacial dysmorphic features (especially hypotelorism), structural CNS anomalies (mainly white matter involvement), conductive hearing loss, seizures, and cardiovascular abnormalities.

The genotypic and phenotypic spectrum of MTO1 deficiency.

PubMed

O'Byrne, James J; Tarailo-Graovac, Maja; Ghani, Aisha; Champion, Michael; Deshpande, Charu; Dursun, Ali; Ozgul, Riza K; Freisinger, Peter; Garber, Ian; Haack, Tobias B; Horvath, Rita; Barić, Ivo; Husain, Ralf A; Kluijtmans, Leo A J; Kotzaeridou, Urania; Morris, Andrew A; Ross, Colin J; Santra, Saikat; Smeitink, Jan; Tarnopolsky, Mark; Wortmann, Saskia B; Mayr, Johannes A; Brunner-Krainz, Michaela; Prokisch, Holger; Wasserman, Wyeth W; Wevers, Ron A; Engelke, Udo F; Rodenburg, Richard J; Ting, Teck Wah; McFarland, Robert; Taylor, Robert W; Salvarinova, Ramona; van Karnebeek, Clara D M

2018-01-01

Mitochondrial diseases, a group of multi-systemic disorders often characterized by tissue-specific phenotypes, are usually progressive and fatal disorders resulting from defects in oxidative phosphorylation. MTO1 (Mitochondrial tRNA Translation Optimization 1), an evolutionarily conserved protein expressed in high-energy demand tissues has been linked to human early-onset combined oxidative phosphorylation deficiency associated with hypertrophic cardiomyopathy, often referred to as combined oxidative phosphorylation deficiency-10 (COXPD10). Thirty five cases of MTO1 deficiency were identified and reviewed through international collaboration. The cases of two female siblings, who presented at 1 and 2years of life with seizures, global developmental delay, hypotonia, elevated lactate and complex I and IV deficiency on muscle biopsy but without cardiomyopathy, are presented in detail. For the description of phenotypic features, the denominator varies as the literature was insufficient to allow for complete ascertainment of all data for the 35 cases. An extensive review of all known MTO1 deficiency cases revealed the most common features at presentation to be lactic acidosis (LA) (21/34; 62% cases) and hypertrophic cardiomyopathy (15/34; 44% cases). Eventually lactic acidosis and hypertrophic cardiomyopathy are described in 35/35 (100%) and 27/34 (79%) of patients with MTO1 deficiency, respectively; with global developmental delay/intellectual disability present in 28/29 (97%), feeding difficulties in 17/35 (49%), failure to thrive in 12/35 (34%), seizures in 12/35 (34%), optic atrophy in 11/21 (52%) and ataxia in 7/34 (21%). There are 19 different pathogenic MTO1 variants identified in these 35 cases: one splice-site, 3 frameshift and 15 missense variants. None have bi-allelic variants that completely inactivate MTO1; however, patients where one variant is truncating (i.e. frameshift) while the second one is a missense appear to have a more severe, even fatal, phenotype. These data suggest that complete loss of MTO1 is not viable. A ketogenic diet may have exerted a favourable effect on seizures in 2/5 patients. MTO1 deficiency is lethal in some but not all cases, and a genotype-phenotype relation is suggested. Aside from lactic acidosis and cardiomyopathy, developmental delay and other phenotypic features affecting multiple organ systems are often present in these patients, suggesting a broader spectrum than hitherto reported. The diagnosis should be suspected on clinical features and the presence of markers of mitochondrial dysfunction in body fluids, especially low residual complex I, III and IV activity in muscle. Molecular confirmation is required and targeted genomic testing may be the most efficient approach. Although subjective clinical improvement was observed in a small number of patients on therapies such as ketogenic diet and dichloroacetate, no evidence-based effective therapy exists. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

SCN3A deficiency associated with increased seizure susceptibility

PubMed Central

Lamar, Tyra; Vanoye, Carlos G.; Calhoun, Jeffrey; Wong, Jennifer C.; Dutton, Stacey B.B.; Jorge, Benjamin S.; Velinov, Milen; Escayg, Andrew; Kearney, Jennifer A.

2017-01-01

Mutations in voltage-gated sodium channels expressed highly in the brain (SCN1A, SCN2A, SCN3A, and SCN8A) are responsible for an increasing number of epilepsy syndromes. In particular, mutations in the SCN3A gene, encoding the pore-forming Nav1.3 α subunit, have been identified in patients with focal epilepsy. Biophysical characterization of epilepsy-associated SCN3A variants suggests that both gain- and loss-of-function SCN3A mutations may lead to increased seizure susceptibility. In this report, we identified a novel SCN3A variant (L247P) by whole exome sequencing of a child with focal epilepsy, developmental delay, and autonomic nervous system dysfunction. Voltage clamp analysis showed no detectable sodium current in a heterologous expression system expressing the SCN3A-L247P variant. Furthermore, cell surface biotinylation demonstrated a reduction in the amount of SCN3A-L247P at the cell surface, suggesting the SCN3A-L247P variant is a trafficking-deficient mutant. To further explore the possible clinical consequences of reduced SCN3A activity, we investigated the effect of a hypomorphic Scn3a allele (Scn3aHyp) on seizure susceptibility and behavior using a gene trap mouse line. Heterozygous Scn3a mutant mice (Scn3a+/Hyp) did not exhibit spontaneous seizures nor were they susceptible to hyperthermia-induced seizures. However, they displayed increased susceptibility to electroconvulsive (6 Hz) and chemiconvulsive (flurothyl and kainic acid) induced seizures. Scn3a+/Hyp mice also exhibited deficits in locomotor activity and motor learning. Taken together, these results provide evidence that loss-of-function of SCN3A caused by reduced protein expression or deficient trafficking to the plasma membrane may contribute to increased seizure susceptibility. PMID:28235671

Epileptic Encephalopathies and Their Relationship to Developmental Disorders: Do Spikes Cause Autism?

ERIC Educational Resources Information Center

Tharp, Barry R.

2004-01-01

Epileptic encephalopathies are progressive clinical and electroencephalographic syndromes where deterioration is thought to be caused by frequent seizures and abundant EEG epileptiform activity. Seizures occur in approximately 10-15% of children with pervasive developmental disorders (PDD) and 8-10% have epileptiform EEG abnormalities without…

[Dandy-Walker variant: Case report].

PubMed

Cueva-Núñez, José E; Lozano-Bustillo, Alejandra; Irias-Álvarez, Merlyn S; Vásquez-Montes, Raúl F; Varela-González, Douglas M

Dandy Walker variant is defined by a variable hypoplasia of the cerebellar vermix with or without posterior fossa increase and without tentorium elevation. describe the case of a rare disease and emphasise the need to clarify the aetiology of prenatal malformations, as well as its multidisciplinary management. A male patient, 8 years of age, with a history of Infantile Cerebral Palsy and epilepsy, who was admitted with a history of tonic-clonic seizures. He was admitted due to psycho-motor developmental delay. During his hospitalisation, he had multiple seizure episodes, controlled with anticonvulsants. A computerized tomography was performed, in which communication was observed between the cisterna magna and fourth ventricle (the latter increased in size). In addition, the cerebellar vermix showed a partial hypoplasia. All these findings were compatible with a variant of the Dandy Walker syndrome. Dandy Walker variant may be asymptomatic and the images found may not indicate them as the cause of developmental disorders, due to its association with multiple syndromes and chromosomal abnormalities. Clinical presentation and prognosis depends on the related disorders, and a multidisciplinary approach is important, because the treatment depends on the symptoms presented. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Incidence of delayed seizures, delayed cerebral ischemia and poor outcome with the use of levetiracetam versus phenytoin after aneurysmal subarachnoid hemorrhage.

PubMed

Karamchandani, Rahul Ramesh; Fletcher, Jeffrey James; Pandey, Aditya Swarup; Rajajee, Venkatakrishna

2014-09-01

Current guidelines recommend against the use of phenytoin following aneurysmal subarachnoid hemorrhage (aSAH) but consider other anticonvulsants, such as levetiracetam, acceptable. Our objective was to evaluate the risk of poor functional outcomes, delayed cerebral ischemia (DCI) and delayed seizures in aSAH patients treated with levetiracetam versus phenytoin. Medical records of patients with aSAH admitted between 2005-2012 receiving anticonvulsant prophylaxis with phenytoin or levetiracetam for >72 hours were reviewed. The primary outcome measure was poor functional outcome, defined as modified Rankin Scale (mRS) score >3 at first recorded follow-up. Secondary outcomes measures included DCI and the incidence of delayed seizures. The association between the use of levetiracetam and phenytoin and the outcomes of interest was studied using logistic regression. Medical records of 564 aSAH patients were reviewed and 259 included in the analysis after application of inclusion/exclusion criteria. Phenytoin was used exclusively in 43 (17%), levetiracetam exclusively in 132 (51%) while 84 (32%) patients were switched from phenytoin to levetiracetam. Six (2%) patients had delayed seizures, 94 (36%) developed DCI and 63 (24%) had mRS score >3 at follow-up. On multivariate analysis, only modified Fisher grade and seizure before anticonvulsant administration were associated with DCI while age, Hunt-Hess grade and presence of intraparenchymal hematoma were associated with mRS score >3. Choice of anticonvulsant was not associated with any of the outcomes of interest. There was no difference in the rate of delayed seizures, DCI or poor functional outcome in patients receiving phenytoin versus levetiracetam after aSAH. The high rate of crossover from phenytoin suggests that levetiracetam may be better tolerated. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Phenotype, biochemical features, genotype and treatment outcome of pyridoxine-dependent epilepsy.

PubMed

Al Teneiji, Amal; Bruun, Theodora U J; Cordeiro, Dawn; Patel, Jaina; Inbar-Feigenberg, Michal; Weiss, Shelly; Struys, Eduard; Mercimek-Mahmutoglu, Saadet

2017-04-01

We report treatment outcome of eleven patients with pyridoxine-dependent epilepsy caused by pathogenic variants in ALDH7A1 (PDE-ALDH7A1). We developed a clinical severity score to compare phenotype with biochemical features, genotype and delays in the initiation of pyridoxine. Clinical severity score included 1) global developmental delay/ intellectual disability; 2) age of seizure onset prior to pyridoxine; 3) current seizures on treatment. Phenotype scored 1-3 = mild; 4-6 = moderate; and 7-9 = severe. Five patients had mild, four patients had moderate, and two patients had severe phenotype. Phenotype ranged from mild to severe in eight patients (no lysine-restricted diet in the infantile period) with more than 10-fold elevated urine or plasma α-AASA levels. Phenotype ranged from mild to moderate in patients with homozygous truncating variants and from moderate to severe in patients with homozygous missense variants. There was no correlation between severity of the phenotype and the degree of α-AASA elevation in urine or genotype. All patients were on pyridoxine, nine patients were on arginine and five patients were on the lysine-restricted diet. 73% of the patients became seizure free on pyridoxine. 25% of the patients had a mild phenotype on pyridoxine monotherapy. Whereas, 100% of the patients, on the lysine-restricted diet initiated within their first 7 months of life, had a mild phenotype. Early initiation of lysine-restricted diet and/or arginine therapy likely improved neurodevelopmental outcome in young patients with PDE-ALDH7A1.

Recurrent seizures, mental retardation and extensive brain calcinosis related to delayed diagnosis of hypoparathyroidism in an adolescent boy.

PubMed

Eom, Tae-Hoon; Kim, Young-Hoon; Kim, Jung-Min

2015-05-01

Reports of adolescent patients presenting with intractable seizures and mental retardation secondary to idiopathic hypothyroidism are uncommon in the literature. In this case, we report a 17-year-old boy who developed recurrent seizures, mental retardation and extensive brain calcinosis related to delayed diagnosis of hypoparathyroidism. Hypoparathyroidism can be easily missed in children and adolescents, and may lead to irreversible neurologic sequelae. This case highlights the need to consider hypocalcemia in any patient with uncontrolled seizures. Copyright © 2015 Elsevier Ltd. All rights reserved.

CDC Kerala 3: At-risk baby clinic service using different screening tools--outcome at 12 months using Developmental Assessment Scale for Indian Infants.

PubMed

Nair, M K C; Krishnan, Rajee; Harikumaran Nair, G S; George, Babu; Bhaskaran, Deepa; Leena, M L; Russell, Paul Swamidhas Sudhakar

2014-12-01

To describe CDC Kerala experience of establishing an at-risk baby clinic and the comparison of different developmental screening tools at 12 mo against the gold standard Developmental Assessment Scale for Indian Infants (DASII). At risk baby clinic of CDC, Kerala was established as a facility for follow up of NICU graduates from Sree Avittam Thirunal Hospital at 2, 4, 6, 8 and 12 mo corrected age and during each visit the mother is taught the CDC model early stimulation by developmental therapists and encouraged to continue to do the same at home. At 12 mo, assessment results of four simple developmental tools were compared with the gold standard DASII administered by a senior developmental therapist. Out of a total of 800 babies, outcome measurements at 12 mo were available for 604 infants. The prevalence of developmental delay using the screening tools, CDC grading for standing, Amiel Tison angles and DDST II (Denver II) gross motor were 24.8, 24 and 24.3% respectively and using DASII, a diagnostic tool (13.3%). Also the combination of Amiel Tison angles, CDC standing grading and DDST gross motor against DASII motor DQ had high specificity (94.15%) and negative predictive value (NPV) (70.18%) but with a very low sensitivity of 14.58% and low positive predictive value (PPV) of 53.85%. It was observed that a significant odds ratio for DASII mental deviation quotient (DQ) was seen for neonatal seizures (2.34) and low birth weight (1.49). The prevalence of developmental delay using the screening tools, CDC grading for standing, Amiel Tison angles and DDST II (Denver II) gross motor were 24.8, 24 and 24.3% respectively and together they had a high specificity, NPV and accuracy against DASII motor DQ as gold standard at one year assessment.

Enhanced oscillatory activity in the hippocampal-prefrontal network is related to short-term memory function after early-life seizures

PubMed Central

Kleen, Jonathan K.; Wu, Edie X.; Holmes, Gregory L.; Scott, Rod C.; Lenck-Santini, Pierre-Pascal

2011-01-01

Neurological insults during development are associated with later impairments in learning and memory. Although remedial training can help restore cognitive function, the neural mechanisms of this recovery in memory systems are largely unknown. To examine this issue we measured electrophysiological oscillatory activity in the hippocampus (both CA3 and CA1) and prefrontal cortex of adult rats that had experienced repeated seizures in the first weeks of life, while they were remedially trained on a delayed-nonmatch-to-sample memory task. Seizure-exposed rats showed initial difficulties learning the task but performed similar to control rats after extra training. Whole-session analyses illustrated enhanced theta power in all three structures while seizure rats learned response tasks prior to the memory task. Whilst performing the memory task, dynamic oscillation patterns revealed that prefrontal cortex theta power was increased among seizure-exposed rats. This enhancement appeared after the first memory training steps using short delays and plateaued at the most difficult steps which included both short and long delays. Further, seizure rats showed enhanced CA1-prefrontal theta coherence in correct trials compared to incorrect trials when long delays were imposed, suggesting increased hippocampal-prefrontal synchrony for the task in this group when memory demand was high. Seizure-exposed rats also showed heightened gamma power and coherence among all three structures during the trials. Our results demonstrate the first evidence of hippocampal-prefrontal enhancements following seizures in early development. Dynamic compensatory changes in this network and interconnected circuits may underpin cognitive rehabilitation following other neurological insults to higher cognitive systems. PMID:22031886

Rubinstein–Taybi syndrome with agenesis of corpus callosum

PubMed Central

Mishra, Shubhankar; Agarwalla, Sunil Kumar; Potpalle, Dnyaneshwar Ramesh; Dash, Nishant Nilotpal

2015-01-01

Rubinstein–Taybi syndrome (RSTS) is a rare genetic disorder with characteristic morphological anomaly. Our patient was a 4.5-year-old girl came with features like broad thumbs, downward slanting palpebral fissures and mental retardation. Systemic abnormalities such as repeated infection, seizure with developmental delay were also associated with it. She was having head banging behavior abnormal slurring speech, incoordination while transferring things from one hand to other. Galaxy of clinical pictures and magnetic resonance imaging report helped to clinch the diagnosis as a case of “RSTS with corpus callosal agenesis” which to the best of our knowledge has never been reported in past from India. PMID:26167229

Microcephaly-capillary malformation syndrome: Brothers with a homozygous STAMBP mutation, uncovered by exome sequencing.

PubMed

Naseer, Muhammad Imran; Sogaty, Sameera; Rasool, Mahmood; Chaudhary, Adeel G; Abutalib, Yousif Ahmed; Walker, Susan; Marshall, Christian R; Merico, Daniele; Carter, Melissa T; Scherer, Stephen W; Al-Qahtani, Mohammad H; Zarrei, Mehdi

2016-11-01

We describe two brothers from a consanguineous family of Egyptian ancestry, presenting with microcephaly, apparent global developmental delay, seizures, spasticity, congenital blindness, and multiple cutaneous capillary malformations. Through exome sequencing, we uncovered a homozygous missense variant in STAMBP (p.K303R) in the two siblings, inherited from heterozygous carrier parents. Mutations in STAMBP are known to cause microcephaly-capillary malformation syndrome (MIC-CAP) and the phenotype in this family is consistent with this diagnosis. We compared the findings in the present brothers with those of earlier reported patients. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Two Siblings With a CDKL5 Mutation: Genotype and Phenotype Evaluation.

PubMed

Hagebeuk, Eveline E O; Marcelis, Carlo L; Alders, Mariëlle; Kaspers, Ageeth; de Weerd, Al W

2015-10-01

This is the second report of a family with a recurrence of a CDKL5 mutation (c. 283-3_290del) in 2 sisters. Both parents tested negative for the mutation in all tissues, but germline mosaicism is likely. Clinically CDKL5 patients resemble those with Rett syndrome, caused by a MECP2 mutation, who experience a regression, after an initial normal development. Even though both siblings showed a typical CDKL5 phenotype, their presentation is different. From birth, the oldest daughter had a severe developmental delay, feeding problems, and hypotonia and experienced daily refractory seizures. The youngest daughter appeared to be normal until age 3 months. At that age seizures started, deterioration and regression became evident, and an epileptic encephalopathy developed. This report of familial recurrence, with suspected germline mosaicism in a healthy parent, has important consequences for genetic counseling. Although it is not possible to predict an exact recurrence risk, it is likely to be increased. © The Author(s) 2015.

Hemimegalencephaly: Clinical, EEG, neuroimaging, and IMP-SPECT correlation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konkol, R.J.; Maister, B.H.; Wells, R.G.

1990-11-01

Iofetamine-single photon emission computed tomography (IMP-SPECT) was performed on 2 girls (5 1/2 and 6 years of age) with histories of intractable seizures, developmental delay, and unilateral hemiparesis secondary to hemimegalencephaly. Electroencephalography (EEG) revealed frequent focal discharges in 1 patient, while a nearly continuous burst suppression pattern over the malformed hemisphere was recorded in the other. IMP-SPECT demonstrated a good correlation with neuroimaging studies. In spite of the different EEG patterns, which had been proposed to predict contrasting clinical outcomes, both IMP-SPECT scans disclosed a similar decrease in tracer uptake in the malformed hemisphere. These results are consistent with themore » pattern of decreased tracer uptake found in other interictal studies of focal seizures without cerebral malformations. In view of recent recommendations for hemispherectomy in these patients, we suggest that the IMP-SPECT scan be used to compliment EEG as a method to define the extent of abnormality which may be more relevant to long-term prognosis than EEG alone.« less

Microglia-Neuron Communication in Epilepsy.

PubMed

Eyo, Ukpong B; Murugan, Madhuvika; Wu, Long-Jun

2017-01-01

Epilepsy has remained a significant social concern and financial burden globally. Current therapeutic strategies are based primarily on neurocentric mechanisms that have not proven successful in at least a third of patients, raising the need for novel alternative and complementary approaches. Recent evidence implicates glial cells and neuroinflammation in the pathogenesis of epilepsy with the promise of targeting these cells to complement existing strategies. Specifically, microglial involvement, as a major inflammatory cell in the epileptic brain, has been poorly studied. In this review, we highlight microglial reaction to experimental seizures, discuss microglial control of neuronal activities, and propose the functions of microglia during acute epileptic phenotypes, delayed neurodegeneration, and aberrant neurogenesis. Future research that would help fill in the current gaps in our knowledge includes epilepsy-induced alterations in basic microglial functions, neuro-microglial interactions during chronic epilepsy, and microglial contribution to developmental seizures. Studying the role of microglia in epilepsy could inform therapies to better alleviate the disease. GLIA 2016;65:5-18. © 2016 Wiley Periodicals, Inc.

The control and prevention of seizures in children, a developmental and environmental approach

NASA Technical Reports Server (NTRS)

Lewinn, E. B.

1978-01-01

The clinical effectiveness of neurophysiological and developmental factors in controlling and preventing seizure mechanisms is detailed. It is shown that as cortical control advances with maturation, it requires increasingly severe environmental adversity to release this residual defensive reflex mechanism. Administration of anticonvulsant drugs is discouraged because of possible undesirable neuronal effects on the very young brain.

Rectal diazepam solution is as good as rectal administration of intravenous diazepam in the first-aid cessation of seizures in children with intractable epilepsy.

PubMed

Chiang, Lin-Mei; Wang, Huei-Shyong; Shen, Hsin-Hsien; Deng, Shin-Tang; Tseng, Chi-Hao; Chen, Yu-In; Chou, Ming-Liang; Hung, Po-Cheng; Lin, Kuang-Lin

2011-02-01

Acute seizures are readily recognizable episodes requiring urgent treatment. This study was conducted to compare the efficacy and safety of suppository use of rectal diazepam solution [Stesolid rectal tube (SRT), Alpharma, Inc., Lierskogen, Norway] with those of intravenous diazepam (IVD), Li Ta Pharma Co, Ltd., Taichung, Taiwan for control of acute seizures in children with intractable epilepsy. Subjects were patients, aged 1-18 years, with intractable epilepsy under at least three kinds of antiepileptic treatments. Caregivers were trained to rectally administer SRT or IVD (dosage varying from 0.2 to 0.5mg per kilogram of body weight) and to monitor respiration condition, seizure severity, and adverse drug effects. Among the 24 subjects, 9 males and 15 females, treated for a period of 3 months, the ages ranged from 2 to 18 years, with a mean of 9.1 years. Seizure types were generalized tonic and/or clonic. Seizure frequency varied from once per week to 20 times per day. Twenty-one (87.5%) of them had mental retardation and/or developmental delay, and 103 of the 127 (81.1%) IVD administrations and 90 of the 103 (87.3%) SRT administrations resulted in rapid cessation of seizures within 10 minutes. Each first dose failed to control seizures in 24 and 13 episodes, respectively. A second dose of IVD achieved cessation of seizure in 21 of the 24 episodes and a second dose of SRT in 12 of the 13 episodes within another 10 minutes. Four episodes (3 with rectal IVD and 1 with SRT) of prolonged seizure beyond 20 minutes needed IVD injection at our emergency room. Sedation occurred in 17% of patients, which was attributed to IVD in 8% and SRT in 9% of patients. No respiratory depression was attributable to IVD or SRT. There was no significant statistical difference in efficacy and safety between these two forms of diazepam. Rectal diazepam solution, administered by capable caregivers, is as effective and safe as rectal administration of IVD for children with intractable epilepsy. Copyright © 2011. Published by Elsevier B.V.

Early neurodevelopmental screening in tuberous sclerosis complex: a potential window of opportunity.

PubMed

Gipson, Tanjala T; Gerner, Gwendolyn; Srivastava, Siddharth; Poretti, Andrea; Vaurio, Rebecca; Hartman, Adam; Johnston, Michael V

2014-09-01

Infants born with tuberous sclerosis complex, a genetic condition resulting from a mutation in TSC1 or TSC2, are at increased risk for intellectual disability and/or autism. Features of epilepsy, neuropathology, genetics, as well as timing and type of mechanism-based medications have been proposed as risk factors. Neurodevelopmental outcomes have been reported among these studies; however, few include data about the individuals' early neurodevelopmental profile, a factor that may contribute significantly to these outcomes. Further, there is no clinical standard for the neurodevelopmental assessment of these infants. The paucity of data regarding the natural history of neurodevelopment in infants with tuberous sclerosis complex and the lack of a gold standard for neurodevelopmental evaluation present a significant challenge for clinicians and researchers. During the first year of life, we tracked the onset of infantile spasms, the type and timing of antiepileptic treatments, and the associated response of two age-matched infants with tuberous sclerosis complex. We also employed Capute Scales as a part of a structured neurodevelopmental evaluation to characterize and compare their neurodevelopmental profiles. Infant 1 developed infantile spasms with confirmed hypsarrhythmia at 4 months of age. Treatment with vigabatrin was initiated within 24 hours with near immediate cessation of seizures and no further seizures to date. Expressive language delay was detected at 12 months and treated with speech and/or language therapy. Infant 2 developed complex partial seizures at 1 month. Treatment included levetiracetam, oxcarbazepine, and the ketogenic diet. Vigabatrin was initiated on detection of hypsarrhythmia after 4 months. Intractable epilepsy persists to date. Global developmental delay was evident by 8 months and treated with physical, occupational, and speech and/or language therapy. Many risk factors have been associated with intellectual disability and/or autism in individuals with tuberous sclerosis complex; however, few data are available regarding practical clinical tools for early identification. In our case series, inclusion of the Capute Scales as a part of routine medical care led to the identification of developmental delays in the first 12 months of life and selection of targeted neurodevelopmental interventions. Development of a risk-based assessment using this approach will be the focus of future studies as it may provide a potential window of opportunity for both research and clinical purposes. In research, it may serve as an objective outcome measure. Clinically, this type of assessment has potential for informing clinical treatment decisions and serving as a prognostic indicator of long-term cognitive and psychiatric outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Neonatal Seizures: An Update on Mechanisms and Management

PubMed Central

Jensen, Frances E.

2010-01-01

The lifespan risk of seizures is highest in the neonatal period. Currently used therapies have limited efficacy. Although the treatment of neonatal seizures has not significantly changed in the last several decades, there has been substantial progress in understanding developmental mechanisms that influence seizure generation and responsiveness to anticonvulsants. Here we provide an overview of current approaches to the diagnosis and treatment of neonatal seizures, identifying some of the recent insights about the pathophysiology of neonatal seizures that may provide the foundation for better treatment. PMID:19944840

Clinical and neuroimaging profile of HIV-1 encephalopathy in infancy and childhood in a sub-Saharan African country.

PubMed

G Mariam, Ayle; Assefa, Getachew

2012-10-01

Neurological dysfunction in AIDS is common, occurring in as many as eighty percent of children. Thus, it is important to recognize the central nervous system imaging appearance of HIV, in particular those of HIV encephalopathy, as this is an AIDS defining illness and with distinct neuro-imaging features essential for early diagnosis and timely therapeutic intervention To identify the clinical features in HIV-1 infection of the central nervous system and their associated neuroradiological correlates. Retrospective review of the records of all children with HIV-1 encephalopathy identified among children with neurological and developmental problems and who were on follow up at a child development and neurology clinic in an African city. A total of 22 children (10 male and 12 female) with HIV-1 encephalopathy were identified among 2382 children with various forms of neurological and developmental problems and who were on follow up at a child development and neurology clinic for a little bit over eight years period. All the children acquired the infection vertically. The age range of these children was between 10 months to 14 years. The median age was 5.6 years. The mean duration of symptom was 3.2 years. Global delay or regression in development along with signs of pyramidal tract involvement and seizures were the commonest clinical signs observed in these children. Neuro-behavioral problems were commonly observed among preschool and school aged children. In older children and preadolescents focal seizures with or with out neurologic deficit and neuroradiological findings were common. Nonhemorrhagic stroke was rare and occurred in one child and another child had cortical blindness. Three children had no neurological deficit. Rapid progression of the disease carried grave prognosis. Opportunistic infections and tumors of the central nervous system were also uncommon among these children. Brain volume loss with dilatation of the lateral ventricle, bilateral symmetrical or asymmetrical calcification of the basal ganglia and periventricular involvement of the white matter were the commonest neuro-radiological findings observed in these children. Atrophy of the brain with dilatation of the lateral ventricles and calcification of the basal ganglia and peri-ventricular involvement of the white matter were the commonest neuro-radiological findings in children with HIV-1 encephalopathy. Similarly global delay or regression in development along with pyramidal tract signs and seizures were the commonest neurological findings. Behavioral problems were common in preschool and school aged children. Focal seizures were common in older children and preadolescents. Rapid progression of the disease carried grave prognosis.

Early seizure detection in an animal model of temporal lobe epilepsy

NASA Astrophysics Data System (ADS)

Talathi, Sachin S.; Hwang, Dong-Uk; Ditto, William; Carney, Paul R.

2007-11-01

The performance of five seizure detection schemes, i.e., Nonlinear embedding delay, Hurst scaling, Wavelet Scale, autocorrelation and gradient of accumulated energy, in their ability to detect EEG seizures close to the seizure onset time were evaluated to determine the feasibility of their application in the development of a real time closed loop seizure intervention program (RCLSIP). The criteria chosen for the performance evaluation were, high statistical robustness as determined through the predictability index, the sensitivity and the specificity of a given measure to detect an EEG seizure, the lag in seizure detection with respect to the EEG seizure onset time, as determined through visual inspection and the computational efficiency for each detection measure. An optimality function was designed to evaluate the overall performance of each measure dependent on the criteria chosen. While each of the above measures analyzed for seizure detection performed very well in terms of the statistical parameters, the nonlinear embedding delay measure was found to have the highest optimality index due to its ability to detect seizure very close to the EEG seizure onset time, thereby making it the most suitable dynamical measure in the development of RCLSIP in rat model with chronic limbic epilepsy.

Clinical profile of infants with hypsarrhythmia.

PubMed

Khreisat, Wael Hayel

2011-09-01

The present study was done in order to obtain a baseline profile of infantile spasms and associated neurological disorders. The study included 50 patients with infantile spasm in Queen Rania Hospital for children in Jordan. The following data were obtained: sex, age at onset of spasms, details of seizure, family history of epilepsy, significant pre-/peri/ post-natal insults, Electroencephalography and detailed neuro imaging evaluation , detailed neurological, neuro developmental ,assessment were done by. Broad categories of possible etiologies were used the results were recorded for further study. Age of onset of infantile spasms ranged from 1month to 1 year and 6 months , (mean 4.8 months). The mean time of presentation was 9.4 months . A male preponderance was noted (74 %). flexor spasms (52%) was the commonest . Other types of seizures also accompanied infantile spasm in 44% children . (84%) were born of normal delivery, History of birth asphyxia was obtained in 48%, 3 (6%) had positive family history Developmental delay was recognized prior to onset of spasms in 52%, microcephaly was the commonest associated problem, Imaging studies of the brain revealed abnormality in 18 patients. 78% patients were classified as symptomatic and 22 % as cryptogenic. the pattern of infantile spasm in our country do not differ from that of developed countries, further researches is required to prevent both chronic epilepsy and psychomotor retardation and .preventive measurement to prevent birth asphyxia is recommended.

Clinical Profile of Infants with Hypsarrhythmia

PubMed Central

Khreisat, Wael Hayel

2011-01-01

Objective: The present study was done in order to obtain a baseline profile of infantile spasms and associated neurological disorders. Patient and methods: The study included 50 patients with infantile spasm in Queen Rania Hospital for children in Jordan. The following data were obtained: sex, age at onset of spasms, details of seizure, family history of epilepsy, significant pre-/peri/ post-natal insults, Electroencephalography and detailed neuro imaging evaluation , detailed neurological, neuro developmental ,assessment were done by. Broad categories of possible etiologies were used the results were recorded for further study. Results: Age of onset of infantile spasms ranged from 1month to 1 year and 6 months , (mean 4.8 months). The mean time of presentation was 9.4 months . A male preponderance was noted (74 %). flexor spasms (52%) was the commonest . Other types of seizures also accompanied infantile spasm in 44% children . (84%) were born of normal delivery, History of birth asphyxia was obtained in 48%, 3 (6%) had positive family history Developmental delay was recognized prior to onset of spasms in 52%, microcephaly was the commonest associated problem, Imaging studies of the brain revealed abnormality in 18 patients. 78% patients were classified as symptomatic and 22 % as cryptogenic. Conclusion: the pattern of infantile spasm in our country do not differ from that of developed countries, further researches is required to prevent both chronic epilepsy and psychomotor retardation and .preventive measurement to prevent birth asphyxia is recommended. PMID:23407582

Novel NR2F1 variants likely disrupt DNA binding: molecular modeling in two cases, review of published cases, genotype–phenotype correlation, and phenotypic expansion of the Bosch–Boonstra–Schaaf optic atrophy syndrome

PubMed Central

Zimmermann, Michael T.; Ferber, Matthew J.; Niu, Zhiyv; Urrutia, Raul A.; Klee, Eric W.; Babovic-Vuksanovic, Dusica

2017-01-01

Bosch–Boonstra–Schaaf optic atrophy syndrome (BBSOAS) is a recently described autosomal dominant disorder caused by mutations in the NR2F1 gene. There are presently 28 cases of BBSOAS described in the literature. Its common features include developmental delay, intellectual disability, hypotonia, optic nerve atrophy, attention deficit disorder, autism spectrum disorder, seizures, hearing defects, spasticity, and thinning of the corpus callosum. Here we report two unrelated probands with novel, de novo, missense variants in NR2F1. The first is a 14-yr-old male patient with hypotonia, intellectual disability, optic nerve hypoplasia, delayed bone age, short stature, and altered neurotransmitter levels on cerebrospinal fluid testing. The second is a 5-yr-old female with severe developmental delay, motor and speech delay, and repetitive motion behavior. Whole-exome sequencing identified a novel missense NR2F1 variant in each case, Cys86Phe in the DNA-binding domain in Case 1, and a Leu372Pro in the ligand-binding domain in Case 2. The presence of clinical findings compatible with BBSOAS along with structural analysis at atomic resolution using homology-based molecular modeling and molecular dynamic simulations, support the pathogenicity of these variants for BBSOAS. Short stature, abnormal CNS neurotransmitters, and macrocephaly have not been previously reported for this syndrome and may represent a phenotypic expansion of BBSOAS. A review of published cases along with new evidence from this report support genotype–phenotype correlations for this disorder. PMID:28963436

Attenuated adenylosuccinate lyase deficiency: a report of one case and a review of the literature.

PubMed

Jurecka, Agnieszka; Zikanova, Marie; Jurkiewicz, Elżbieta; Tylki-Szymańska, Anna

2014-02-01

We present a 9-year follow-up of a patient with an attenuated (type II) adenylosuccinate lyase deficiency with no obvious signs of disease progression and degradation. We also review the literature, focusing on attenuated phenotype, and we report a positive effect of a ketogenic diet on seizure control. The patient presented at the age of 5 months with a history of global developmental delay. Screening of urinary purine metabolites revealed elevation of succinyladenosine and succinylaminoimidazolecarboxamide riboside (a ratio of 2:1). Mutation analysis revealed a compound heterozygosity for missense mutations: p.R426H and p.D268H. She began to walk independently at the age of 3 years. From the age of 4 years, her communication skills improved and she presented fewer autistic features. Due to poor results in seizure control, the ketogenic diet was introduced at the age of 7 years, resulting in reduction of seizure frequency. Currently, at the age of 9 years, the girl is attending a special kindergarten and is functioning very well in her preschool group. She began to make statements that form a logical continuity and make progress in simple manual operations. The patient participates in therapies such as pet therapy, hippotherapy, speech therapy, physiotherapy, hydrotherapy, and music therapy. Georg Thieme Verlag KG Stuttgart · New York.

Is it juvenile myoclonic epilepsy?

PubMed

Gelisse, P; Genton, P; Raybaud, C; Thomas, P; Bartolomei, F; Dravet, C

2000-03-01

A 21-year old man with marked developmental delay was referred for the diagnosis of myoclonic jerks (MJ), which were sometimes responsible for sudden falls without loss of consciousness, that had begun 2 years before, and for a recent generalized tonic-clonic seizure preceded by a cluster of MJ. Physical examination revealed a small stature, bilateral pyramidal signs, severe mental retardation, and retinis pigmentosa. Etiological factors for this encephalopathy were not found (muscle and skin biopsies, karyotype and extensive blood chemistry). Waking interictal EEG showed a normal background activity and generalized poly-spike-and wave (PSW) discharges. Photic stimulation disclosed a marked photoparoxysmal response, sometimes associated with myoclonic jerks. Three spontaneous jerks accompanied by a burst of generalized PSW were recorded on awakening from a nap. The MRI disclosed wide ventricles, a thin corpus callosum, brainstem atrophy and a so-called "redundant gyration"; these changes were evocative of acquired perinatal damage. Juvenile myoclonic epilepsy (JME) was diagnosed and valproate was started resulting in complete control of seizures. During a 5-year follow-up, the patient has remained seizure-free and the EEG consistently normal. In our opinion, JME can be diagnosed in very uncommon settings, including patients with significant brain damage, as long as all the other criteria for the diagnosis are present.

Evaluation of the effect of jobelyn(®) on chemoconvulsants-induced seizure in mice.

PubMed

Umukoro, Solomon; Omogbiya, Itivere Adrian; Eduviere, Anthony Taghogho

2013-01-01

Epilepsy is a common central nervous system (CNS) disorder characterized by seizures resulting from episodic neuronal discharges. The incidence of toxicity and refractoriness has compromised the clinical efficacy of the drugs currently used for the treatment of convulsions. Thus, there is a need to search for new medicines from plant origin that are readily available and safer for the control of seizures. Jobelyn(®) (JB) is a unique African polyherbal preparation used by the natives to treat seizures in children. This investigation was carried out to evaluate whether JB has anti-seizure property in mice. The animals received JB (5, 10 and 20 mg/kg, p.o) 30 min before induction of convulsions with intraperitoneal (i.p.) injection of picotoxin (6 mg/kg), strychnine (2 mg/kg) and pentylenetetrazole (85 mg/kg) respectively. Diazepam (2 mg/kg, p.o.) was used as the reference drug. Anti-seizure activities were assessed based on the ability of test drugs to prevent convulsions, death or to delay the onset of seizures in mice. JB (5, 10 and 20 mg/kg, p.o) could only delay the onset of seizures induced by pentylenetetrazole (85 mg/kg, i.p.) in mice. However, it did not did not offer any protection against seizure episodes, as it failed to prevent the animals, from exhibiting tonic-clonic convulsions caused by pentylenetetrazole (85 mg/kg, i.p.), strychnine (2 mg/kg) or picrotoxin (6 mg/kg, i.p.). On the other hand, diazepam (2 mg/kg, i.p.), offered 100% protection against convulsive seizures, induced by pentylenetetrazole (85 mg/kg, i.p.). However, it failed to prevent seizures produced by strychnine (2 mg/kg, i.p.) or picrotoxin (6 mg/kg, i.p.). Our results suggest that JB could not prevent the examined chemoconvulsants-induced convulsions. However, its ability to delay the latency to seizures induced by pentylenetetrazole suggests that JB might be effective in the control of the seizure spread in epileptic brains.

Temporal lobe neoplasm and seizures: how deep does the story go?

PubMed

Jehi, Lara E; Lüders, Hans O; Naugle, Richard; Ruggieri, Paul; Morris, Harold; Foldvary, Nancy; Wyllie, Elaine; Kotagal, Prakash; Bingaman, Bill; Dinner, Dudley; Prayson, Richard; Diehl, Beate; Alexopoulos, Andreas; Bautista, Jocelyn; Busch, Robyn

2008-03-01

[March 2008-Cleveland Case Report]. There is a well-described association between the occurrence of developmental tumors and the presence of cortical dysplasia in the neighboring brain tissue. The main surgical approaches in the treatment of medically refractory epilepsy related to such developmental tumors include a lesionectomy versus a tailored cortical resection, often guided by an invasive evaluation. This case report describes the surgical management of a 26-year-old female with olfactory auras evolving into automotor seizures and convulsions, occurring in the context of a right temporo-parietal developmental lesion. It illustrates the pros and cons of various surgical approaches, and discusses some pathophysiological aspects of developmental tumors, dysplasia and epilepsy. [Published with video sequences].

Nephrogenic diabetes insipidus with intracranial calcification in a child with thalassemia minor.

PubMed

Dimple, Jain; Alka, Jadhav; Mona, Gajre; Atul, Deshmukh

2013-09-01

There are numerous causes for intracranial calcification in children. We describe an unusual cause of intracranial calcification in a child, namely, nephrogenic diabetes insipidus (NDI). A 12-year-old boy presented with seizures and developmental delay. MRI of the brain revealed intracranial calcification. Evaluation showed findings suggestive of NDI. The lack of evidence of any other metabolic defect suggests that these calcifications were secondary to NDI. He also had anemia for which he was investigated and diagnosed as thalassemia minor. Detailed literature review failed to reveal any reported association between NDI and thalassemia minor. We report this case to emphasize the importance of early diagnosis and treatment of NDI to prevent organic brain damage.

Febrile Seizures and Behavioural and Cognitive Outcomes in Preschool Children: The Generation R Study

ERIC Educational Resources Information Center

Visser, Annemarie M.; Jaddoe, Vincent W. V.; Ghassabian, Akhgar; Schenk, Jacqueline J.; Verhulst, Frank C.; Hofman, Albert; Tiemeier, Henning; Moll, Henriette A.; Arts, Willem Frans M.

2012-01-01

Aim: General developmental outcome is known to be good in school-aged children who experienced febrile seizures. We examined cognitive and behavioural outcomes in preschool children with febrile seizures, including language and executive functioning outcomes. Method: This work was performed in the Generation R Study, a population-based cohort…

Causes of death in remote symptomatic epilepsy.

PubMed

Day, S M; Wu, Y W; Strauss, D J; Shavelle, R M; Reynolds, R J

2005-07-26

To determine the causes of death of individuals with developmental disabilities that occur more frequently among those with remote symptomatic epilepsy (i.e., epilepsy occurring in persons with developmental delay or identified brain lesions) than for those without. The authors compared causes of mortality in persons with (n = 10,030) and without (n = 96,163) history of epilepsy in a California population of persons with mild developmental disabilities, 1988 to 2002. Subjects had traumatic brain injury, cerebral palsy, Down syndrome, autism, or a developmental disability with other or unknown etiology. There were 721,759 person-years of data, with 2,397 deaths. Underlying causes of death were determined from the State of California's official mortality records. Cause-specific death rates and standardized mortality ratios (SMRs) were computed for those with and without epilepsy relative to subjects in the California general population. Comparisons were then made between SMRs of those with and without epilepsy, and CIs on the ratios of SMRs were determined. Death rates for persons with epilepsy were elevated for several causes. The greatest excess was due to seizures (International Classification of Diseases-9 [ICD-9] 345; SMR 53.1, 95% CI 28.0 to 101.0) and convulsions (ICD-9 780.3; SMR 25.2, 95% CI 11.7 to 54.2). Other causes occurring more frequently in those with epilepsy included brain cancer (SMR 5.2, 95% CI 2.2 to 12.1), respiratory diseases (SMR 1.7, 95% CI 1.2 to 2.5), circulatory diseases (SMR 1.3, 95% CI 1.0 to 1.7), and accidents (SMR 2.7, 95% CI 1.9 to 3.7), especially accidental drowning (SMR 12.8, 95% CI 7.0 to 23.2). Remote symptomatic epilepsy is associated with an increased risk of death. Seizures, aspiration pneumonia, and accidental drowning are among the leading contributors.

Towards acute pediatric status epilepticus intervention teams: Do we need "Seizure Codes"?

PubMed

Stredny, Coral M; Abend, Nicholas S; Loddenkemper, Tobias

2018-05-01

To identify areas of treatment delay and barriers to care in pediatric status epilepticus, review ongoing quality improvement initiatives, and provide suggestions for further innovations to improve and standardize these patient care processes. Narrative review of current status epilepticus management algorithms, anti-seizure medication administration and outcomes associated with delays, and initiatives to improve time to treatment. Articles reviewing or reporting quality improvement initiatives were identified through a PubMed search with keywords "status epilepticus," "quality improvement," "guideline adherence," and/or "protocol;" references of included articles were also reviewed. Rapid initiation and escalation of status epilepticus treatment has been associated with shortened seizure duration and more favorable outcomes. Current evidence-based guidelines for management of status epilepticus propose medication algorithms with suggested times for each management step. However, time to antiseizure medication administration for pediatric status epilepticus remains delayed in both the pre- and in-hospital settings. Barriers to timely treatment include suboptimal preventive care, inaccurate seizure detection, infrequent or restricted use of home rescue medications by caregivers and pre-hospital emergency personnel, delayed summoning and arrival of emergency personnel, and use of inappropriately dosed medications. Ongoing quality improvement initiatives in the pre- and in-hospital settings targeting these barriers are reviewed. Improved preventive care, seizure detection, and rescue medication education may advance pre-hospital management, and we propose the use of acute status epilepticus intervention teams to initiate and incorporate in-hospital interventions as time-sensitive "Seizure Code" emergencies. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Familial Congenital Unilateral Cerebral Ventriculomegaly: Delineation of a Distinct Genetic Disorder

PubMed Central

Zaki, Maha S.; Afifi, Hanan H.; Barkovich, AJ.; Gleeson, Joseph G.

2016-01-01

We identified two female siblings, derived from healthy first cousin parents, with congenital unilateral cerebral ventriculomegaly detected prenatally. Patient 1 underwent ventriculoperitoneal shunt operation at 1 week old, while Patient 2 was followed without surgical intervention. Both patients presented with mild developmental delay and hemiparesis contralateral to the involved hemisphere. Focal seizures were observed in Patient 1, whose neuroimaging revealed posterior insular polymicrogyria in the normal sized ventricle hemisphere and retrocerebellar cyst. Both siblings displayed near absence of white matter with marked thinning of the overlying cortex in the affected hemisphere and very thin corpus callosum. Investigations revealed no other system involvement and karyotyping was normal. Normal TORCH screening in subsequent pregnancies, normal parental coagulation profile and undetectable maternal autoantibodies suggested against the possible role of extrinsic factors as an etiological factor for unilateral ventriculomegaly. Parents had normal brain imaging findings. We suggest delineation of a distinct developmental brain defect, most likely of autosomal recessive inheritance. PMID:19610102

Longitudinal changes in seizure outcomes after resection of cerebral cavernous malformations in patients presenting with seizures: a long-term follow-up of 46 patients.

PubMed

Kim, Jiha; Kim, Chi Heon; Chung, Chun Kee

2014-08-01

Seizure is the most common presentation in patients with cerebral cavernous malformations (CCMs). Although many articles have documented seizure outcomes after resection of CCM, few have conducted long-term follow-ups; thus, the fluctuating seizure outcomes have been neglected. The purpose of this study is to describe long-term postoperative seizure outcomes in patients with CCM and to compare seizure outcomes between patients with sporadic seizures and those with chronic seizures. Forty-six patients with CCM presenting with seizures underwent surgery. The male-to-female ratio was 1:1, and the average age at initial seizure onset was 27.6 years. The mean preoperative seizure duration was 42.7 months. Patients were divided into two groups: a chronic group (N = 20) and a sporadic group (N = 26) according to seizure frequency and duration. The mean postoperative follow-up duration was 96.3 months, and the postoperative seizure outcomes were checked annually based upon Engel's classification. After the first year of follow-up, 80.8 % of the sporadic group and 75.0 % of the chronic group were evaluated as Engel class I. These rates increased to 100.0 % and 90.0 %, respectively, at the eighth year of follow-up. Overall, 29 (63.0 %) of the 46 patients experienced changes in seizure outcomes over the follow-up period. Despite their delayed improvements, the chronic group showed less favorable outcomes throughout follow-up (p = 0.025). Long-term follow-up is indispensable for accurately assessing postoperative seizure outcomes because these outcomes change continuously. We recommend earlier surgery to achieve seizure-free status in patients with CCM. However, even in the chronic group, surgery is recommended, considering the overall delayed improvement.

Long-Term Neurodevelopmental Outcome of Neonates with Hypernatremic Dehydration.

PubMed

Boskabadi, Hassan; Akhondian, Javad; Afarideh, Maliheh; Maamouri, Gholamali; Bagheri, Sepideh; Parizadeh, Seyyed Mostafa; Mobarhan, Majid Ghayour; Mohammadi, Shabnam; Frens, Gordon A A

2017-04-01

Neonatal hypernatremic dehydration (NHD) is a dangerous condition that can lead to severe weight loss, renal impairment, and central nervous system complications. We aimed to evaluate the consequences of NHD in infants in their second year of life. This was a prospective case-control study in Ghaem hospital, Mashhad, Iran. Sixty-five healthy breastfed neonates (serum sodium concentration <150 mmol/L) and 65 hypernatremic (serum sodium concentration ≥150 mmol/L) neonates were followed up from 2008 to 2011. Maternal and neonatal factors were compared between the two groups together with their growth parameters, and developmental milestones (using Denver II developmental assessment scores) were assessed and compared in ages 6, 12, 18, and 24 months, respectively. The weight of infants at 6 months of age was significantly different between the two groups (7,264 ± 1,089 g vs. 7,596 ± 957 g, p = 0.009). Twenty-five percent of infants in the group who had developed NHD had a delay in development at 6 months of age, with corresponding values of 21% at 12 months, 19% at 18 months, and 12% at 24 months of age. Developmental delay was ∼0.3% for the control group at similar ages. The severity of hypernatremia was strongly correlated with poor developmental outcome at 6 months (p = 0.001). Serum sodium concentration of neonates was 153-195 mg/dL in the NHD group. Median peak serum sodium was 158 ± 16 in case group and 141 ± 9 in control group. Serious complications were cerebral edema (five cases), hemorrhage (five cases), and kidney stones (six cases). Hypernatremic dehydration has an adverse effect on child development especially in the first year of life, their prevalence decreases with advanced age. Growth problems are also present during their first year of life. The major signs and symptoms of infants with poor prognosis on admission were poor feeding (8 infants, 61.5%), seizure (3 infants, 23.1%), hyperthermia (1 infant, 7.7%), and lethargy (1 infant, 7.7%). NHD affects growth parameters and developmental milestones of children. Occasionally the child's weight gain was normalized by the end of first year of life; although developmental delay continued, its severity was reduced, with age.

The promise of subtraction ictal SPECT co-registered to MRI for improved seizure localization in pediatric epilepsies: Affecting factors and relationship to the surgical outcome

PubMed Central

Stamoulis, Catherine; Verma, Nishant; Kaulas, Himanshu; Halford, Jonathan J.; Duffy, Frank H.; Pearl, Phillip L.; Treves, S. Ted

2016-01-01

Objective Ictal SPECT is promising for accurate non-invasive localization of the epileptogenic brain tissue in focal epilepsies. However, high quality ictal scans require meticulous attention to the seizure onset. In a relatively large cohort of pediatric patients, this study investigated the impact of the timing of radiotracer injection, MRI findings and seizure characteristics on ictal SPECT localizations, and the relationship between concordance of ictal SPECT, scalp EEG and resected area with seizure freedom following epilepsy surgery. Methods Scalp EEG and ictal SPECT studies from 95 patients (48 males and 47 females, median age = 11 years, (25th, 75th) quartiles = (6.0, 14.75) years) with pharmacoresistant focal epilepsy and no prior epilepsy surgery were reviewed. The ictal SPECT result was examined as a function of the radiotracer injection delay, seizure duration, epilepsy etiology, cerebral lobe of seizure onset identified by EEG and MRI findings. Thirty two patients who later underwent epilepsy surgery had postoperative seizure freedom data at <1, 6 and 12 months. Results Sixty patients (63.2%) had positive SPECT localizations - 51 with a hyperperfused region that was concordant with the cerebral lobe of seizure origin identified by EEG and 9 with discordant localizations. Of these, 35 patients (58.3%) had temporal and 25 (41.7%) had extratemporal seizures. The ictal SPECT result was significantly correlated with the injection delay (p<0.01) and cerebral lobe of seizure onset (specifically frontal versus temporal; p = 0.02) but not MRI findings (p = 0.33), epilepsy etiology (p ≥ 0.27) or seizure duration (p = 0.20). Concordance of SPECT, scalp EEG and resected area was significantly correlated with seizure freedom at 6 months after surgery (p=0.04). Significance Ictal SPECT holds promise as a powerful source imaging tool for presurgical planning in pediatric epilepsies. To optimize the SPECT result the radiotracer injection delay should be minimized to ≤ 25 s, although the origin of seizure onset (specifically temporal versus frontal) also significantly impacts the localization. PMID:27918961

The promise of subtraction ictal SPECT co-registered to MRI for improved seizure localization in pediatric epilepsies: Affecting factors and relationship to the surgical outcome.

PubMed

Stamoulis, Catherine; Verma, Nishant; Kaulas, Himanshu; Halford, Jonathan J; Duffy, Frank H; Pearl, Phillip L; Treves, S Ted

2017-01-01

Ictal SPECT is promising for accurate non-invasive localization of the epileptogenic brain tissue in focal epilepsies. However, high quality ictal scans require meticulous attention to the seizure onset. In a relatively large cohort of pediatric patients, this study investigated the impact of the timing of radiotracer injection, MRI findings and seizure characteristics on ictal SPECT localizations, and the relationship between concordance of ictal SPECT, scalp EEG and resected area with seizure freedom following epilepsy surgery. Scalp EEG and ictal SPECT studies from 95 patients (48 males and 47 females, median age=11years, (25th, 75th) quartiles=(6.0, 14.75) years) with pharmacoresistant focal epilepsy and no prior epilepsy surgery were reviewed. The ictal SPECT result was examined as a function of the radiotracer injection delay, seizure duration, epilepsy etiology, cerebral lobe of seizure onset identified by EEG and MRI findings. Thirty two patients who later underwent epilepsy surgery had postoperative seizure freedom data at <1, 6 and 12 months. Sixty patients (63.2%) had positive SPECT localizations - 51 with a hyperperfused region that was concordant with the cerebral lobe of seizure origin identified by EEG and 9 with discordant localizations. Of these, 35 patients (58.3%) had temporal and 25 (41.7%) had extratemporal seizures. The ictal SPECT result was significantly correlated with the injection delay (p<0.01) and cerebral lobe of seizure onset (specifically frontal versus temporal; p=0.02) but not MRI findings (p=0.33), epilepsy etiology (p≥0.27) or seizure duration (p=0.20). Concordance of SPECT, scalp EEG and resected area was significantly correlated with seizure freedom at 6 months after surgery (p=0.04). Ictal SPECT holds promise as a powerful source imaging tool for presurgical planning in pediatric epilepsies. To optimize the SPECT result the radiotracer injection delay should be minimized to≤25s, although the origin of seizure onset (specifically temporal versus frontal) also significantly impacts the localization. Copyright © 2016 Elsevier B.V. All rights reserved.

Microdeletion/microduplication of proximal 15q11.2 between BP1 and BP2: a susceptibility region for neurological dysfunction including developmental and language delay.

PubMed

Burnside, Rachel D; Pasion, Romela; Mikhail, Fady M; Carroll, Andrew J; Robin, Nathaniel H; Youngs, Erin L; Gadi, Inder K; Keitges, Elizabeth; Jaswaney, Vikram L; Papenhausen, Peter R; Potluri, Venkateswara R; Risheg, Hiba; Rush, Brooke; Smith, Janice L; Schwartz, Stuart; Tepperberg, James H; Butler, Merlin G

2011-10-01

The proximal long arm of chromosome 15 has segmental duplications located at breakpoints BP1-BP5 that mediate the generation of NAHR-related microdeletions and microduplications. The classical Prader-Willi/Angelman syndrome deletion is flanked by either of the proximal BP1 or BP2 breakpoints and the distal BP3 breakpoint. The larger Type I deletions are flanked by BP1 and BP3 in both Prader-Willi and Angelman syndrome subjects. Those with this deletion are reported to have a more severe phenotype than individuals with either Type II deletions (BP2-BP3) or uniparental disomy 15. The BP1-BP2 region spans approximately 500 kb and contains four evolutionarily conserved genes that are not imprinted. Reports of mutations or disturbed expression of these genes appear to impact behavioral and neurological function in affected individuals. Recently, reports of deletions and duplications flanked by BP1 and BP2 suggest an association with speech and motor delays, behavioral problems, seizures, and autism. We present a large cohort of subjects with copy number alteration of BP1 to BP2 with common phenotypic features. These include autism, developmental delay, motor and language delays, and behavioral problems, which were present in both cytogenetic groups. Parental studies demonstrated phenotypically normal carriers in several instances, and mildly affected carriers in others, complicating phenotypic association and/or causality. Possible explanations for these results include reduced penetrance, altered gene dosage on a particular genetic background, or a susceptibility region as reported for other areas of the genome implicated in autism and behavior disturbances.

Limbic control of aggression in the cat.

PubMed

Adamec, R E; Stark-Adamec, C I

1983-01-01

Over a decade of work by Flynn and colleagues has delineated a network of limbic circuits which function to modulate the expression of predatory aggression and defence in the cat, and aspects of this work are reviewed. In particular, Flynn's work revealed a circuit involving the basomedial amygdala which functions to suppress attack, and at the same time facilitates defence. A second circuit, involving the ventral hippocampus, is involved in attack facilitation. Studies relating stable differences in excitability in these two circuits to developmentally determined behavioural dispositions toward aggression or defence are summarized. Finally, the impact of experimentally induced limbic seizures on interictally maintained expression of aggression and defence behaviourally, and on limbic excitability are reviewed. Taken together, the data indicate that the behavioural balance of attack and defence is under the tonic control of opponent limbic circuits, which are themselves biased in a measureable manner. Developmental studies indicate that adult defensiveness is determined early in life, so early as to suggest some pre-programmed neuro-developmental process. Experimentally induced seizures alter behaviour lastingly, producing an increase in defensive disposition. At the same time there is an equally lasting potentiation of interictal transmission of neural activity from the amygdala to the hypothalamus. Moreover, seizures may reduce interictal transmission of activity through the ventral hippocampus by potentiating recurrent inhibition. These effects of seizures are of interest since seizures reproduce naturally occurring differences in limbic excitability seen in naturally defensive cats.

Heterozygous truncation mutations of the SMC1A gene cause a severe early onset epilepsy with cluster seizures in females: Detailed phenotyping of 10 new cases.

PubMed

Symonds, Joseph D; Joss, Shelagh; Metcalfe, Kay A; Somarathi, Suresh; Cruden, Jamie; Devlin, Anita M; Donaldson, Alan; DiDonato, Nataliya; Fitzpatrick, David; Kaiser, Frank J; Lampe, Anne K; Lees, Melissa M; McLellan, Ailsa; Montgomery, Tara; Mundada, Vivek; Nairn, Lesley; Sarkar, Ajoy; Schallner, Jens; Pozojevic, Jelena; Parenti, Ilaria; Tan, Jeen; Turnpenny, Peter; Whitehouse, William P; Zuberi, Sameer M

2017-04-01

The phenotype of seizure clustering with febrile illnesses in infancy/early childhood is well recognized. To date the only genetic epilepsy consistently associated with this phenotype is PCDH19, an X-linked disorder restricted to females, and males with mosaicism. The SMC1A gene, which encodes a structural component of the cohesin complex is also located on the X chromosome. Missense variants and small in-frame deletions of SMC1A cause approximately 5% of Cornelia de Lange Syndrome (CdLS). Recently, protein truncating mutations in SMC1A have been reported in five females, all of whom have been affected by a drug-resistant epilepsy, and severe developmental impairment. Our objective was to further delineate the phenotype of SMC1A truncation. Female cases with de novo truncation mutations in SMC1A were identified from the Deciphering Developmental Disorders (DDD) study (n = 8), from postmortem testing of an affected twin (n = 1), and from clinical testing with an epilepsy gene panel (n = 1). Detailed information on the phenotype in each case was obtained. Ten cases with heterozygous de novo mutations in the SMC1A gene are presented. All 10 mutations identified are predicted to result in premature truncation of the SMC1A protein. All cases are female, and none had a clinical diagnosis of CdLS. They presented with onset of epileptic seizures between <4 weeks and 28 months of age. In the majority of cases, a marked preponderance for seizures to occur in clusters was noted. Seizure clusters were associated with developmental regression. Moderate or severe developmental impairment was apparent in all cases. Truncation mutations in SMC1A cause a severe epilepsy phenotype with cluster seizures in females. These mutations are likely to be nonviable in males. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

[Glucose transponer type 1 deficiency síndrome (GLUT-1 SD) treated with ketogenic diet. Report of one case].

PubMed

Cornejo, Verónica E; Cabello, Juan Francisco A; Colombo, Marta C; Raimann, Erna B

2007-05-01

The glucose transporter type 1 deficiency syndrome (GLUT-1 SD) (OMIM 606777) is an inborn error of metabolism of brain glucose transport. The characteristic clinical manifestations are seizures, hypotonia, developmental delay, microcephaly and hypoglycorrhachia. We report a girl with normal weight and height at birth. At 6 weeks of age she started with convulsions reaching up to 20 myoclonic seizures a day. She was treated with valproate, phenobarbital and carbamazepine without response. Blood analysis including aminoacids and acylcarnitines were all normal. The brain MRI showed frontal atrophy with an increased subarachnoidal space and Electroencephalography was abnormal. Blood glucose was 84 mg/dl and spinal fluid glucose 26 mg/dl with a ratio of 0.31 (Normal Ratio >0.65+/-00.1). These results suggested the diagnosis of GLUT-1 SD, and was confirmed with erythrocyte glucose uptake of 44% (Normal range 80-100%). A molecular study found the mutation 969del, C971T in exon 6 of the gene Glut-1. Treatment with a ketogenic diet was started immediately and after 7 days with this diet seizures ceased. Anticonvulsants were progressively suspended. At present, the patient is 6 years old, she continues on a ketogenic diet and supplements with L-carnitine, lipoic acid, vitamins and minerals. Growth and development are normal with an intelligence quotient of 103. It is concluded that it is necessary to include GLUT-1 SD in the differential diagnosis of children with early seizures that are non responsive to pharmacological treatment.

Pattern of Corticospinal Projections Defined by Brain Mapping During Resective Epilepsy Surgery in a Patient with Congenital Hemiparesis and Intractable Epilepsy.

PubMed

Yang, Chen-Ya; Chen, Hsin-Hung; Chen, Chien; Chiu, Jan-Wei; Chou, Chen-Liang; Yang, Tsui-Fen

2017-11-01

Congenital or early-onset brain structural lesions often cause contralateral hemiparesis, cognitive deficits, developmental delays, and seizures. Seizure is the most debilitating condition, as it greatly impairs quality of life in both the affected individuals and their caregivers and prevents them from active social participation. A 34-year-old man with hemiparesis and early-onset seizures since childhood owing to a congenital brain lesion developed intractable seizures in the last 2 years and was subsequently admitted for resective epileptic surgery. During the operation, we employed an innovative intraoperative neurophysiologic monitoring technique. In contrast to routine application for transcranial stimulation, we recorded compound muscle action potentials over the bilateral limb muscles simultaneously, instead of over the contralateral muscles only, to determine the patterns of the corticospinal projections. Transcranial stimulation over the bilateral hemispheres was applied before craniotomy, and direct cortical stimulation over the lesioned hemisphere was applied after craniotomy. By integrating both approaches, we could first identify the pattern of corticospinal projections before craniotomy and then accurately define the noneloquent area, which guided the resection to successfully accomplish the surgical goal. This technique is simple because no patient participation is required. We believe that it has the potential to replace conventional preoperative functional magnetic resonance imaging and transcranial magnetic stimulation in resective epilepsy surgery, particularly for young patients. Not only can it improve the safety of surgical procedures, but also it can help predict functional outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Lived experience of epilepsy from the perspective of children in Taiwan.

PubMed

Chen, Hsiu-Jung; Chen, Yueh-Chih; Yang, Hui-Chuan; Chi, Ching-Shiang

2010-05-01

The purpose of this study was to explore the lived experiences of school-aged children with epilepsy in Taiwan. Epilepsy affects many people worldwide, especially school-aged children, but few studies have examined children's viewpoints of their experiences with epilepsy. An exploratory, phenomenological interview design was used. Children (ages 7-12 years) with well-controlled epilepsy and no developmental delay were recruited from a hospital in central Taiwan. Data were collected from 15 children using a semi-structured interview guide. Interviews were tape-recorded with permission from parents and children. Verbatim transcripts were analysed using Colazzi's phenomenological method. Two themes emerged from the analysis. The first theme, 'living with epilepsy', had two subthemes: disease-related experiences and school-related issues. The second theme, 'coping with epilepsy', had two subthemes: developing strategies to manage or reduce seizures and seeking support from family members. Taiwanese children with epilepsy had similar lived experiences as their counterparts in Western culture, e.g. unpleasant somatic symptoms, difficulty learning and troubled peer relationships. Taiwanese children also coped similarly with epilepsy by taking medications to control seizures, but they differed from their Western counterparts in trying to self-manage seizures and seeking support from family members. Public health and school nurses can apply our findings to educate school teachers and parents about epilepsy and encourage activities that allow children with and without epilepsy to interact, thus improving peer relationships and reducing stigmatisation. Children with and without epilepsy would also benefit from an age-appropriate education manual that includes causes of epilepsy, treatment, dealing with seizures and psychological and social adaptation.

Significant Sleep Dysregulation in a Toddler With Developmental Delay.

PubMed

Stein, Martin T; Owens, Judith; Abbott, Myles

Derrick's parents made an appointment with a new pediatrician for a second opinion about disordered sleep. Now 22-months old, he was evaluated at 18 months of age for developmental delay when he was found to have "a regulatory disorder associated with delays in language and motor development, hypotonia and significant sleep problems." The parents are now most concerned about his sleeping pattern. Prolonged sleep onset and frequent night awaking occur each night since 6-months of age. These problems are more severe in the past few months when he awakes screaming and cannot be settled. The awakening episodes occur 2 to 4 times each night when "he screams and thrashes his body for up to an hour." Daytime tantrums increased. After the parents read a book about sleep in young children, they provided a calm atmosphere at bedtime including a dark room and singing a quiet lullaby. When these changes did not alter sleep, they purchased a vibrating mattress which was also unsuccessful.Derrick was born full term after an uncomplicated prenatal and perinatal course. He sat at 10 months, crawled at 12 months, and walked at 18 months. He currently drinks from a sippy cup and he can use a utensil to eat. He has few words saying only "no" and "mama" in the past month. Imitation of some words occurred recently. He has responded to simple directions in the past 2 months. Derrick passed the newborn audiology screen. He does not have difficulty swallowing and he does not drool. He plays with many different toys and he plays in parallel with his older brother who also experienced delays in motor and language development. His brother is now doing very well in school. There is no family history of cognitive delay, seizure disorder, cerebral palsy, early developmental delay (other than the brother) or a significant sleep problem. PHYSICAL EXAMINATION:: head circumference, length and weight (75th percentile). He had mild generalized hypotonia, mild weakness, 2+ symmetrical deep tendon reflexes, and absence of ankle clonus. His gait was slightly wide based, steady, and without a limp. Neither ataxia nor drooling was observed. He was easily engaged in play with the examiner without evidence of irritability. The remainder of the examination was normal.

Pitt-Hopkins Syndrome: A Review of Current Literature, Clinical Approach, and 23-Patient Case Series.

PubMed

Goodspeed, Kimberly; Newsom, Cassandra; Morris, Mary Ann; Powell, Craig; Evans, Patricia; Golla, Sailaja

2018-03-01

Pitt-Hopkins syndrome (PTHS) is a rare, genetic disorder caused by a molecular variant of TCF4 which is involved in embryologic neuronal differentiation. PTHS is characterized by syndromic facies, psychomotor delay, and intellectual disability. Other associated features include early-onset myopia, seizures, constipation, and hyperventilation-apneic spells. Many also meet criteria for autism spectrum disorder. Here the authors present a series of 23 PTHS patients with molecularly confirmed TCF4 variants and describe 3 unique individuals. The first carries a small deletion but does not exhibit the typical facial features nor the typical pattern of developmental delay. The second exhibits typical facial features, but has attained more advanced motor and verbal skills than other reported cases to date. The third displays typical features of PTHS, however inherited a large chromosomal duplication involving TCF4 from his unaffected father with somatic mosaicism. To the authors' knowledge, this is the first chromosomal duplication case reported to date.

Inner retinal dystrophy in a patient with biallelic sequence variants in BRAT1.

PubMed

Oatts, Julius T; Duncan, Jacque L; Hoyt, Creig S; Slavotinek, Anne M; Moore, Anthony T

2017-12-01

Mutations in the BRCA1-associated protein required for the ataxia telangiectasia mutated (ATM) activation-1 (BRAT1) gene cause lethal neonatal rigidity and multifocal seizure syndrome characterized by rigidity and intractable seizures and a milder phenotype with intellectual disability, seizures, nonprogressive cerebellar ataxia or dyspraxia, and cerebellar atrophy. To date, nystagmus, cortical visual impairment, impairment of central vision, optic nerve hypoplasia, and optic atrophy have been described in this condition. This article describes the retinal findings in a patient with biallelic deleterious sequence variants in BRAT1. Case report of a child with biallelic sequence variants in the BRAT1 gene. This patient had developmental delay, microcephaly, nystagmus, and esotropia, and full-field electroretinography (ERG) revealed an inner retinal dystrophy. She was found on exome sequencing to have compound heterozygous sequence variants in the BRAT1 gene: one maternally inherited frameshift variant (c.294dupA, predicting p.Leu99Thrfs*92), which has previously been reported, and one paternally inherited novel missense variant (c.803G>A, p.Arg268His), which is likely to affect protein function. Biallelic sequence variants in BRAT1 have been reported to cause a variety of ocular and systemic manifestations, but to our knowledge, this is the first report of inner retinal dysfunction manifest as selective loss of full-field ERG scotopic and photopic b-wave amplitudes.

Severe early-onset epileptic encephalopathy due to mutations in the KCNA2 gene: Expansion of the genotypic and phenotypic spectrum.

PubMed

Hundallah, Khaled; Alenizi, Asma'a; AlHashem, Amal; Tabarki, Brahim

2016-07-01

Recently, de novo loss- or gain-of-function mutations in the KCNA2 gene; have been described in individuals with epileptic encephalopathy, ataxia or intellectual disability. In this report, we describe a further case of KCNA2-early-onset epileptic encephalopathy. The patient presented since birth with intractable seizures, progressive microcephaly, developmental delay, and progressive brain atrophy. Whole-exome sequencing showed a novel de novo mutation in the KCNA2 gene: c.1120A > G (p.Thr374Ala). This case expands the genotypic and phenotypic disease spectrum of this genetic form of KCNA2-early onset epileptic encephalopathy. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Embolization of congenital intrahepatic porto-systemic shunt by n-butyl cyanoacrylate.

PubMed

Gupta, Vivek; Kalra, Naveen; Vyas, Sameer; Sodhi, K S; Thapa, B R; Khandelwal, N

2009-10-01

Congenital intrahepatic portosystemic venous shunt (IHPSVS) is rare vascular anomaly. We present one case of a 14-month male child who presented with global developmental delay. Child had high ammonia levels with low glutamine and high bile salts on the previous investigations and had history of neonatal seizures since day 13 of life. On admission, serum ammonia levels were elevated to 112micromol/L. Other laboratory investigations including liver and renal function test, and electrolytes were normal. He was, diagnosed to have IHPSVS on the basis of Doppler and CT, and treated by embolization with n-butyl cyanoacrylate (glue). A brief review of diagnostic modalities and endovascular management for the IHPSVS is presented including the present case.

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

PubMed

Patel, Jaina; Mercimek-Mahmutoglu, Saadet

2016-10-01

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.

The effect of acute aripiprazole treatment on chemically and electrically induced seizures in mice: The role of nitric oxide.

PubMed

Shafaroodi, Hamed; Oveisi, Simin; Hosseini, Mahsa; Niknahad, Hossein; Moezi, Leila

2015-07-01

Aripiprazole is an antipsychotic drug which acts through dopamine and serotonin receptors. Aripiprazole was noted to have antiseizure effects in a study on mice, while it induced seizures in a few human case reports. Dopaminergic and serotonergic systems relate to nitric oxide, and aripiprazole also has effects on dopamine and serotonin receptors. This study investigated the effects of aripiprazole on seizures and the potential role of nitric oxide in the process. The following three models were examined to explore the role of aripiprazole on seizures in mice: 1 - pentylenetetrazole administered intravenously, 2 - pentylenetetrazole administered intraperitoneally, and 3 - electroshock. Aripiprazole administration delayed clonic seizure in intravenous and intraperitoneal pentylenetetrazole models. In the electroshock-induced seizure model, tonic seizure and mortality protection percent were increased after aripiprazole administration. In intraperitoneal administration of pentylenetetrazole, aripiprazole effects on clonic seizure latency were significantly decreased when l-NAME - a nonselective nitric oxide synthase (NOS) inhibitor, 7-nitroindazole - a selective neuronal NOS (nNOS) inhibitor, or aminoguanidine - a selective inducible NOS (iNOS) inhibitor was injected before aripiprazole administration. In the intravenous pentylenetetrazole method, administration of l-NAME or aminoguanidine inhibited aripiprazole effects on clonic seizure threshold. Aminoguanidine or l-NAME administration decreased aripiprazole-induced protection against tonic seizures and death in the electroshock model. In both intravenous and intraperitoneal seizure models, aripiprazole and l-arginine coadministration delayed the onset of clonic seizures. Moreover, it increased protection against tonic seizures and death in intraperitoneal pentylenetetrazole and electroshock models. In conclusion, the release of nitric oxide via iNOS or nNOS may be involved in anticonvulsant properties of aripiprazole. Copyright © 2015 Elsevier Inc. All rights reserved.

Differentiation of Speech Delay and Global Developmental Delay in Children Using DTI Tractography-Based Connectome.

PubMed

Jeong, J-W; Sundaram, S; Behen, M E; Chugani, H T

2016-06-01

Pure speech delay is a common developmental disorder which, according to some estimates, affects 5%-8% of the population. Speech delay may not only be an isolated condition but also can be part of a broader condition such as global developmental delay. The present study investigated whether diffusion tensor imaging tractography-based connectome can differentiate global developmental delay from speech delay in young children. Twelve children with pure speech delay (39.1 ± 20.9 months of age, 9 boys), 14 children with global developmental delay (39.3 ± 18.2 months of age, 12 boys), and 10 children with typical development (38.5 ± 20.5 months of age, 7 boys) underwent 3T DTI. For each subject, whole-brain connectome analysis was performed by using 116 cortical ROIs. The following network metrics were measured at individual regions: strength (number of the shortest paths), efficiency (measures of global and local integration), cluster coefficient (a measure of local aggregation), and betweeness (a measure of centrality). Compared with typical development, global and local efficiency were significantly reduced in both global developmental delay and speech delay (P < .0001). The nodal strength of the cognitive network is reduced in global developmental delay, whereas the nodal strength of the language network is reduced in speech delay. This finding resulted in a high accuracy of >83% ± 4% to discriminate global developmental delay from speech delay. The network abnormalities identified in the present study may underlie the neurocognitive and behavioral consequences commonly identified in children with global developmental delay and speech delay. Further validation studies in larger samples are required. © 2016 by American Journal of Neuroradiology.

Anticonvulsant activity of Cotyledon orbiculata L. (Crassulaceae) leaf extract in mice.

PubMed

Amabeoku, G J; Green, I; Kabatende, J

2007-05-30

The anticonvulsant activity of Cotyledon orbiculata L. (Crassulaceae) was investigated by studying the effects of both aqueous and methanol extracts of the plant species on seizures induced by pentylenetetrazole, bicuculline, picrotoxin and N-methyl-dl-aspartic in mice. Aqueous extract of Cotyledon orbiculata (50-400mg/kg, i.p.) and methanol extract (100-400mg/kg, i.p.) significantly prolonged the onset of tonic seizures induced by pentylenetetrazole (95mg/kg, i.p.). Methanol extract (400mg/kg, i.p.) also significantly reduced the incidence of the seizures. One hundred to two hundred milligrams/kilogram (i.p.) of aqueous extract of Cotyledon orbiculata significantly delayed the onset of the tonic seizures induced by bicuculline (40mg/kg, i.p.), picrotoxin (12mg/kg, i.p.) and N-methyl-dl-aspartic acid (NMDLA, 400mg/kg, i.p.). Similarly, methanol extract (100-400mg/kg, i.p.) significantly delayed the onset of the tonic seizures induced by bicuculline (40mg/kg, i.p.) and picrotoxin (12mg/kg, i.p.) while 100mg/kg (i.p.) significantly delayed the onset of N-methyl-dl-aspartic acid (NMDLA, 400mg/kg, i.p.)-induced seizures. Methanol extract (200mg/kg, i.p.) significantly reduced the incidence of the seizures induced by bicuculline (40mg/kg, i.p.). Phenobarbitone (12mg/kg, i.p.) and diazepam (0.5mg/kg, i.p.) effectively antagonized only seizures induced by PTZ (95mg/kg, i.p.), bicuculline (40mg/kg, i.p.) and picrotoxin (12mg/kg, i.p.). Phenytoin (30mg/kg, i.p.) did not affect any of the seizures to any significant extent. The data obtained suggest that both aqueous and methanol extracts of Cotyledon orbiculata have anticonvulsant property and may probably be affecting both gabaergic and glutaminergic mechanisms to exert its effect. The phytochemical analysis carried out revealed the presence of cardiac glycosides, saponins, tannins, reducing sugar and triterpene steroids in the plant extract.

Development and characterization of a mouse with profound biotinidase deficiency: a biotin-responsive neurocutaneous disorder.

PubMed

Pindolia, Kirit; Jordan, Megan; Guo, Caiying; Matthews, Nell; Mock, Donald M; Strovel, Erin; Blitzer, Miriam; Wolf, Barry

2011-02-01

Biotinidase deficiency is the primary enzymatic defect in biotin-responsive, late-onset multiple carboxylase deficiency. Untreated children with profound biotinidase deficiency usually exhibit neurological symptoms including lethargy, hypotonia, seizures, developmental delay, sensorineural hearing loss and optic atrophy; and cutaneous symptoms including skin rash, conjunctivitis and alopecia. Although the clinical features of the disorder markedly improve or are prevented with biotin supplementation, some symptoms, once they occur, such as developmental delay, hearing loss and optic atrophy, are usually irreversible. To prevent development of symptoms, the disorder is screened for in the newborn period in essentially all states and in many countries. In order to better understand many aspects of the pathophysiology of the disorder, we have developed a transgenic biotinidase-deficient mouse. The mouse has a null mutation that results in no detectable serum biotinidase activity or cross-reacting material to antibody prepared against biotinidase. When fed a biotin-deficient diet these mice develop neurological and cutaneous symptoms, carboxylase deficiency, mild hyperammonemia, and exhibit increased urinary excretion of 3-hydroxyisovaleric acid and biotin and biotin metabolites. The clinical features are reversed with biotin supplementation. This biotinidase-deficient animal can be used to study systematically many aspects of the disorder and the role of biotinidase, biotin and biocytin in normal and in enzyme-deficient states. Copyright © 2010 Elsevier Inc. All rights reserved.

Developmental Toxic Effects of Exposure to Chemical Warfare Nerve Agents in Rats: Effects on Brain and Behavior

DTIC Science & Technology

2014-10-01

stimulation of acetylcholine receptors. Common consequences of this cholinergic crisis include seizure activity, neuronal damage and behavioral deficits. The...recurrent seizures (SRS) were observed. The current results demonstrate the vulnerability of a juvenile population to motor impairments, cognitive deficits...spontaneous recurrent seizures compared to adult rats (data not shown), which may lead to more extensive neuropathology. In addition, a small

Developmental Exposure to PCBs Differentially Alters Sensitivity to Audiogenic and Kindling-Induced Seizures in Rats

EPA Science Inventory

Previously we reported an increased incidence of audiogenic seizures in offspring of pregnant rats exposed to an environmental mixture of polychlorinated biphenyls (PCBs). This study compares the proconvulsant properties of PCB exposure in audiogenic and electrical kindling seizu...

Comparison of the Intramuscular, Intranasal or Sublingual Routes of Midazolam Administration for the Control of Soman-Induced Seizures

DTIC Science & Technology

2008-01-01

23, 2008) Abstract: This study evaluated the anticonvulsant effectiveness of midazolam to stop seizures elicited by the nerve agent soman when...seizure activity that was detected in the electroencephalographic record. When given immediately after seizure onset, the anticonvulsant ED 50 of...that time. At the 40-min. treatment delay, the anticonvulsant ED 50 s of intramuscular or intranasal midazolam did not differ and both were

Individualised prediction model of seizure recurrence and long-term outcomes after withdrawal of antiepileptic drugs in seizure-free patients: a systematic review and individual participant data meta-analysis.

PubMed

Lamberink, Herm J; Otte, Willem M; Geerts, Ada T; Pavlovic, Milen; Ramos-Lizana, Julio; Marson, Anthony G; Overweg, Jan; Sauma, Letícia; Specchio, Luigi M; Tennison, Michael; Cardoso, Tania M O; Shinnar, Shlomo; Schmidt, Dieter; Geleijns, Karin; Braun, Kees P J

2017-07-01

People with epilepsy who became seizure-free while taking antiepileptic drugs might consider discontinuing their medication, with the possibility of increased quality of life because of the elimination of adverse events. The risk with this action, however, is seizure recurrence. The objectives of our study were to identify predictors of seizure recurrence and long-term seizure outcomes and to produce nomograms for estimation of individualised outcomes. We did a systematic review and meta-analysis, and identified eligible articles and candidate predictors, using PubMed and Embase databases with a last update on Nov 6, 2014. Eligible articles had to report on cohorts of patients with epilepsy who were seizure-free and had started withdrawal of antiepileptic drugs; articles also had to contain information regarding seizure recurrences during and after withdrawal. We excluded surgical cohorts, reports with fewer than 30 patients, and reports on acute symptomatic seizures because these topics were beyond the scope of our objective. Risk of bias was assessed using the Quality in Prognosis Studies system. Data analysis was based on individual participant data. Survival curves and proportional hazards were computed. The strongest predictors were selected with backward selection. Models were converted to nomograms and a web-based tool to determine individual risks. We identified 45 studies with 7082 patients; ten studies (22%) with 1769 patients (25%) were included in the meta-analysis. Median follow-up was 5·3 years (IQR 3·0-10·0, maximum 23 years). Prospective and retrospective studies and randomised controlled trials were included, covering non-selected and selected populations of both children and adults. Relapse occurred in 812 (46%) of 1769 patients; 136 (9%) of 1455 for whom data were available had seizures in their last year of follow-up, suggesting enduring seizure control was not regained by this timepoint. Independent predictors of seizure recurrence were epilepsy duration before remission, seizure-free interval before antiepileptic drug withdrawal, age at onset of epilepsy, history of febrile seizures, number of seizures before remission, absence of a self-limiting epilepsy syndrome, developmental delay, and epileptiform abnormality on electroencephalogram (EEG) before withdrawal. Independent predictors of seizures in the last year of follow-up were epilepsy duration before remission, seizure-free interval before antiepileptic drug withdrawal, number of antiepileptic drugs before withdrawal, female sex, family history of epilepsy, number of seizures before remission, focal seizures, and epileptiform abnormality on EEG before withdrawal. Adjusted concordance statistics were 0·65 (95% CI 0·65-0·66) for predicting seizure recurrence and 0·71 (0·70-0·71) for predicting long-term seizure freedom. Validation was stable across the individual study populations. We present evidence-based nomograms with robust performance across populations of children and adults. The nomograms facilitate prediction of outcomes following drug withdrawal for the individual patient, including both the risk of relapse and the chance of long-term freedom from seizures. The main limitations were the absence of a control group continuing antiepileptic drug treatment and a consistent definition of long-term seizure freedom. Epilepsiefonds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Patterns of postictal cerebral perfusion in idiopathic generalized epilepsy: a multi-delay multi-parametric arterial spin labelling perfusion MRI study.

PubMed

Chen, Guangxiang; Lei, Du; Ren, Jiechuan; Zuo, Panli; Suo, Xueling; Wang, Danny J J; Wang, Meiyun; Zhou, Dong; Gong, Qiyong

2016-07-04

The cerebral haemodynamic status of idiopathic generalized epilepsy (IGE) is a very complicated process. Little attention has been paid to cerebral blood flow (CBF) alterations in IGE detected by arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI). However, the selection of an optimal delay time is difficult for single-delay ASL. Multi-delay multi-parametric ASL perfusion MRI overcomes the limitations of single-delay ASL. We applied multi-delay multi-parametric ASL perfusion MRI to investigate the patterns of postictal cerebral perfusion in IGE patients with absence seizures. A total of 21 IGE patients with absence seizures and 24 healthy control subjects were enrolled. IGE patients exhibited prolonged arterial transit time (ATT) in the left superior temporal gyrus. The mean CBF of IGE patients was significantly increased in the left middle temporal gyrus, left parahippocampal gyrus and left fusiform gyrus. Prolonged ATT in the left superior temporal gyrus was negatively correlated with the age at onset in IGE patients. This study demonstrated that cortical dysfunction in the temporal lobe and fusiform gyrus may be related to epileptic activity in IGE patients with absence seizures. This information can play an important role in elucidating the pathophysiological mechanism of IGE from a cerebral haemodynamic perspective.

Respiratory and sleep disorders in female children with atypical Rett syndrome caused by mutations in the CDKL5 gene.

PubMed

Hagebeuk, Eveline E O; van den Bossche, Renilde A S; de Weerd, Al W

2013-05-01

In female children with drug-resistant seizures and developmental delay from birth, atypical Rett syndrome caused by mutations in the CDKL5 gene should be considered. Several clinical features resemble classic Rett syndrome. Respiratory and sleep abnormalities are frequently present in Rett syndrome, whereas little is known in patients with CDKL5 mutations. In four genetically confirmed female patients with CDKL5 mutations (age range 2-15 y), the presence of breathing and sleep abnormalities was evaluated using the validated Sleep Disturbance Scale for Children and polysomnography (PSG). The Sleep Disturbance Scale for Children indicated disorders of initiating and maintaining sleep, daytime somnolence, and sleep breathing disorders. In one patient, PSG showed central apnoeas during sleep: her total apnoea-hypopnoea index (AHI) was 4.9, of which the central AHI was 3.4/h. When awake, central apnoeas were present in two of the four female children (central AHI 28/h and 41/h respectively), all preceded by hyperventilation. PSG showed low rapid eye movement (REM) sleep (9.7-18.3%), frequent awakenings, and low sleep efficiency (range 59-78%). Episodic hyperventilation followed by central apnoeas was present while awake in two of four patients. This may indicate failure of brainstem respiratory centres. In addition, low REM sleep, frequent arousals (not caused by apnoeas/seizures), and low sleep efficiency were present. Similar to Rett syndrome, in patients with CDKL5 mutations PSG seems warranted to evaluate breathing and sleep disturbances. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

Not all SCN1A epileptic encephalopathies are Dravet syndrome: Early profound Thr226Met phenotype.

PubMed

Sadleir, Lynette G; Mountier, Emily I; Gill, Deepak; Davis, Suzanne; Joshi, Charuta; DeVile, Catherine; Kurian, Manju A; Mandelstam, Simone; Wirrell, Elaine; Nickels, Katherine C; Murali, Hema R; Carvill, Gemma; Myers, Candace T; Mefford, Heather C; Scheffer, Ingrid E

2017-09-05

To define a distinct SCN1A developmental and epileptic encephalopathy with early onset, profound impairment, and movement disorder. A case series of 9 children were identified with a profound developmental and epileptic encephalopathy and SCN1A mutation. We identified 9 children 3 to 12 years of age; 7 were male. Seizure onset was at 6 to 12 weeks with hemiclonic seizures, bilateral tonic-clonic seizures, or spasms. All children had profound developmental impairment and were nonverbal and nonambulatory, and 7 of 9 required a gastrostomy. A hyperkinetic movement disorder occurred in all and was characterized by dystonia and choreoathetosis with prominent oral dyskinesia and onset from 2 to 20 months of age. Eight had a recurrent missense SCN1A mutation, p.Thr226Met. The remaining child had the missense mutation p.Pro1345Ser. The mutation arose de novo in 8 of 9; for the remaining case, the mother was negative and the father was unavailable. Here, we present a phenotype-genotype correlation for SCN1A . We describe a distinct SCN1A phenotype, early infantile SCN1A encephalopathy, which is readily distinguishable from the well-recognized entities of Dravet syndrome and genetic epilepsy with febrile seizures plus. This disorder has an earlier age at onset, profound developmental impairment, and a distinctive hyperkinetic movement disorder, setting it apart from Dravet syndrome. Remarkably, 8 of 9 children had the recurrent missense mutation p.Thr226Met. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Delayed seizure associated with paclitaxel-Cremophor el in a patient with early-stage breast cancer.

PubMed

O'Connor, Tracey L; Kossoff, Ellen

2009-08-01

Paclitaxel, a microtubule stabilizer, is an effective agent for treating cancer of the breast, ovary, head and neck, and lung. Because paclitaxel is insoluble in water, it is formulated with the micelle-forming Cremophor EL. Neurologic toxicity is well described with both the drug and this carrier, with most toxicities manifesting as peripheral neuropathy, motor neuropathy, autonomic neuropathy, and myopathy. Toxic effects on the central nervous system, such as seizures or encephalopathy, have been rarely reported; however, the seizures reported were closely related to the time of infusion. We describe a 41-year-old woman with no history of seizures who was treated with paclitaxel for breast cancer. Four days after the drug was infused, she developed a generalized tonic-clonic seizure that could not be attributed to other causes. The patient was treated with phenytoin and was able to complete her adjuvant chemotherapy with nab-paclitaxel without further events. Her condition was neurologically stable without phenytoin for the next 6 months. Use of the Naranjo adverse drug reaction probability scale indicated a possible association (score of 3) between the delayed seizure and paclitaxel or its solvent, Cremophor EL. Clinicians should be aware of the potential for seizure activity in patients who receive paclitaxel formulated with Cremophor EL.

Seizures and epilepsy in hypoglycaemia caused by inborn errors of metabolism.

PubMed

Gataullina, Svetlana; Delonlay, Pascale; Lemaire, Eric; Boddaert, Nathalie; Bulteau, Christine; Soufflet, Christine; Laín, Gemma Aznar; Nabbout, Rima; Chiron, Catherine; Dulac, Olivier

2015-02-01

The aim of the study was to characterize seizures and epilepsy related to hypoglycaemia. We analyzed the files of 170 consecutive patients referred for hypoglycaemia (onset 1h to 4y) caused by inborn errors of metabolism (glycogen storage disease type I, fatty acid β-oxidation disorders, and hyperinsulinism). Ninety patients (42 males and 48 females; 38 neonates and 52 infants/children) had brief hypoglycaemic seizures (68%) or status epilepticus (32%). Status epilepticus occurred earlier (mean 1.4d) than brief neonatal seizures (4.3d, p=0.02). Recurrent status epilepticus followed initial status epilepticus and was often triggered by fever. Epilepsy developed in 21 patients. In 18 patients, epilepsy followed hypoglycaemic status epilepticus and began with shorter delay when associated with grey matter lesions (1.9mo, standard error of the mean [SEM] 1mo) than with white matter damage (3.3y [SEM 1y], p=0.003). Three patients with hyperinsulinism developed idiopathic epilepsy following brief neonatal seizures. Brief neonatal hyperinsulinaemic hypoglycaemic seizures have characteristics of idiopathic neonatal seizures. Neonatal status epilepticus should be prevented by the systematic measurement of glucose blood level. Recurrent seizures never consist of status epilepticus when following brief initial seizures. Epilepsy is symptomatic of brain damage with shorter delay in the case of grey rather than white matter lesions, except in a few idiopathic cases in which epilepsy and hyperinsulinism may share a common genetic background. © 2014 Mac Keith Press.

Spoken language outcomes after hemispherectomy: factoring in etiology.

PubMed

Curtiss, S; de Bode, S; Mathern, G W

2001-12-01

We analyzed postsurgery linguistic outcomes of 43 hemispherectomy patients operated on at UCLA. We rated spoken language (Spoken Language Rank, SLR) on a scale from 0 (no language) to 6 (mature grammar) and examined the effects of side of resection/damage, age at surgery/seizure onset, seizure control postsurgery, and etiology on language development. Etiology was defined as developmental (cortical dysplasia and prenatal stroke) and acquired pathology (Rasmussen's encephalitis and postnatal stroke). We found that clinical variables were predictive of language outcomes only when they were considered within distinct etiology groups. Specifically, children with developmental etiologies had lower SLRs than those with acquired pathologies (p =.0006); age factors correlated positively with higher SLRs only for children with acquired etiologies (p =.0006); right-sided resections led to higher SLRs only for the acquired group (p =.0008); and postsurgery seizure control correlated positively with SLR only for those with developmental etiologies (p =.0047). We argue that the variables considered are not independent predictors of spoken language outcome posthemispherectomy but should be viewed instead as characteristics of etiology. Copyright 2001 Elsevier Science.

Effects of JIP3 on epileptic seizures: Evidence from temporal lobe epilepsy patients, kainic-induced acute seizures and pentylenetetrazole-induced kindled seizures.

PubMed

Wang, Z; Chen, Y; Lü, Y; Chen, X; Cheng, L; Mi, X; Xu, X; Deng, W; Zhang, Y; Wang, N; Li, J; Li, Y; Wang, X

2015-08-06

JNK-interacting protein 3 (JIP3), also known as JNK stress-activated protein kinase-associated protein 1 (JSAP1), is a scaffold protein mainly involved in the regulation of the pro-apoptotic signaling cascade mediated by c-Jun N-terminal kinase (JNK). Overexpression of JIP3 in neurons in vitro has been reported to lead to accelerated activation of JNK and enhanced apoptosis response to cellular stress. However, the occurrence and the functional significance of stress-induced modulations of JIP3 levels in vivo remain elusive. In this study, we investigated the expression of JIP3 in temporal lobe epilepsy (TLE) and in a kainic acid (KA)-induced mouse model of epileptic seizures, and determined whether down-regulation of JIP3 can decrease susceptibility to seizures and neuron damage induced by KA. We found that JIP3 was markedly increased in TLE patients and a mouse model of epileptic seizures; mice underexpressing JIP3 through lentivirus bearing LV-Letm1-RNAi showed decreased susceptibility, delayed first seizure and decreased seizure duration response to the epileptogenic properties of KA. Subsequently, a decreased activation of JNK following seizure induction was observed in mice underexpressing JIP3, which also exhibited less neuronal apoptosis in the CA3 region of the hippocampus, as assessed three days after KA administration. We also found that mice underexpressing JIP3 exhibited a delayed pentylenetetrazole (PTZ)-induced kindling seizure process. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Developmental tumors and adjacent cortical dysplasia: single or dual pathology?

PubMed

Palmini, André; Paglioli, Eliseu; Silva, Vinicius Duval

2013-12-01

Developmental tumors often lead to refractory partial seizures and constitute a well-defined, surgically remediable epilepsy syndrome. Dysplastic features are often associated with these tumors, and their significance carries both practical and conceptual relevance. If associated focal cortical dysplasia (FCD) relates to the extent of the epileptogenic tissue, then presurgical evaluation and surgical strategies should target both the tumor and the surrounding dyslaminated cortex. Furthermore, the association has been included in the recently revised classification of FCD and the epileptogenicity of this associated dysplastic tissue is crucial to validate such revision. In addition to the possibility of representing dual pathology, the association of developmental tumors and adjacent dysplasia may instead represent a single developmental lesion with distinct parts distributed along a histopathologic continuum. Moreover, the possibility that this adjacent dyslamination is of minor epileptogenic relevance should also be entertained. Surgical data show that complete resection of the solid tumors and immediately adjacent tissue harboring satellites may disrupt epileptogenic networks and lead to high rates of seizure freedom, challenging the epileptogenic relevance of more extensive adjacent dyslaminated cortex. Whether the latter is a primary or secondary abnormality and whether dyslaminated cortex in the context of a second lesion may produce seizures after complete resection of the main lesion is still to be proven. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Novel CDKL5 Mutations in Czech Patients with Phenotypes of Atypical Rett Syndrome and Early-Onset Epileptic Encephalopathy.

PubMed

Záhoráková, D; Langová, M; Brožová, K; Laštůvková, J; Kalina, Z; Rennerová, L; Martásek, P

2016-01-01

The X-linked CDKL5 gene, which encodes cyclin-dependent kinase-like 5 protein, has been implicated in early-onset encephalopathy and atypical Rett syndrome with early-onset seizures. The CDKL5 protein is a kinase required for neuronal development and morphogenesis, but its precise functions are still largely unexplored. Individuals with CDKL5 mutations present with severe global developmental delay, intractable epilepsy, and Rett-like features. A clear genotype-phenotype correlation has not been established due to an insufficient number of reported cases. The aim of this study was to analyse the CDKL5 gene in Czech patients with early-onset seizures and Rett-like features. We performed mutation screening in a cohort of 83 individuals using high-resolution melting analysis, DNA sequencing and multiplex ligation- dependent probe amplification. Molecular analyses revealed heterozygous pathogenic mutations in three girls with severe intellectual disability and intractable epilepsy starting at the age of two months. All three identified mutations, c.637G>A, c.902_977+29del105, and c.1757_1758delCT, are novel, thus significantly extending the growing spectrum of known pathogenic CDKL5 sequence variants. Our results support the importance of genetic testing of the CDKL5 gene in patients with early-onset epileptic encephalopathy and Rett-like features with early-onset seizures. This is the first study referring to molecular defects of CDKL5 in Czech cases.

Novel images extraction model using improved delay vector variance feature extraction and multi-kernel neural network for EEG detection and prediction.

PubMed

Ge, Jing; Zhang, Guoping

2015-01-01

Advanced intelligent methodologies could help detect and predict diseases from the EEG signals in cases the manual analysis is inefficient available, for instance, the epileptic seizures detection and prediction. This is because the diversity and the evolution of the epileptic seizures make it very difficult in detecting and identifying the undergoing disease. Fortunately, the determinism and nonlinearity in a time series could characterize the state changes. Literature review indicates that the Delay Vector Variance (DVV) could examine the nonlinearity to gain insight into the EEG signals but very limited work has been done to address the quantitative DVV approach. Hence, the outcomes of the quantitative DVV should be evaluated to detect the epileptic seizures. To develop a new epileptic seizure detection method based on quantitative DVV. This new epileptic seizure detection method employed an improved delay vector variance (IDVV) to extract the nonlinearity value as a distinct feature. Then a multi-kernel functions strategy was proposed in the extreme learning machine (ELM) network to provide precise disease detection and prediction. The nonlinearity is more sensitive than the energy and entropy. 87.5% overall accuracy of recognition and 75.0% overall accuracy of forecasting were achieved. The proposed IDVV and multi-kernel ELM based method was feasible and effective for epileptic EEG detection. Hence, the newly proposed method has importance for practical applications.

Behavior Problems in Toddlers with and without Developmental Delays: Comparison of Treatment Outcomes

ERIC Educational Resources Information Center

Holtz, Casey A.; Carrasco, Jennifer M.; Mattek, Ryan J.; Fox, Robert A.

2009-01-01

The purpose of this study is to examine the effectiveness of an in-home parent management program for toddlers with behavior problems and developmental delays by comparing outcomes for a group of toddlers with developmental delays (n = 27) and a group of toddlers without developmental delays (n = 27). The majority of children lived in single…

Toddler Developmental Delays After Extensive Hospitalization: Primary Care Practitioner Guidelines.

PubMed

Lehner, Dana C; Sadler, Lois S

2015-01-01

This review investigated developmental delays toddlers may encounter after a lengthy pediatric hospitalization (30 days or greater). Physical, motor, cognitive, and psychosocial development of children aged 1 to 3 years was reviewed to raise awareness of factors associated with developmental delay after extensive hospitalization. Findings from the literature suggest that neonatal and pediatric intensive care unit (NICU/PICU) graduates are most at risk for developmental delays, but even non-critical hospital stays interrupt development to some extent. Primary care practitioners (PCPs) may be able to minimize risk for delays through the use of formal developmental screening tests and parent report surveys. References and resources are described for developmental assessment to help clinicians recognize delays and to educate families about optimal toddler development interventions. Pediatric PCPs play a leading role in coordinating health and developmental services for the young child following an extensive hospital stay.

A Comparison of Motor Delays in Young Children: Autism Spectrum Disorder, Developmental Delay, and Developmental Concerns

ERIC Educational Resources Information Center

Provost, Beth; Lopez, Brian R.; Heimerl, Sandra

2007-01-01

This study assessed motor delay in young children 21-41 months of age with autism spectrum disorder (ASD), and compared motor scores in children with ASD to those of children without ASD. Fifty-six children (42 boys, 14 girls) were in three groups: children with ASD, children with developmental delay (DD), and children with developmental concerns…

Pediatric Susceptibility to Nerve Agent-Induced Seizures and Effectiveness of Anticonvulsant Treatments

DTIC Science & Technology

2014-12-01

poisoning can result in status epilepticus (SE), which can become pharmacoresistant if treatment is delayed. Virtually no data exist on OP-induced...are needed to characterize models of P7 and P14 DFP-induced SE. 15. SUBJECT TERMS Status Epilepticus , seizure, organophosphate, DFP, pediatric...5 Introduction Organophosphate (OP) exposure can lead to continuous, repetitive seizures (i.e., status epilepticus , SE), which are

Developmental Dyscalculia and Medical Assessment.

ERIC Educational Resources Information Center

Shalev, Ruth S.; Gross-Tsur, Varda

1993-01-01

Medical evaluation of seven third-grade children with developmental dyscalculia in a mainstream setting identified neurological conditions (including petit mal seizures, Gerstmann syndrome, and attention deficit disorder without hyperactivity) in all the children. Findings suggest that children who are not improving academically should undergo…

Developmental delays and dental caries in low-income preschoolers in the USA: a pilot cross-sectional study and preliminary explanatory model

PubMed Central

2013-01-01

Background Anecdotal evidence suggests that low-income preschoolers with developmental delays are at increased risk for dental caries and poor oral health, but there are no published studies based on empirical data. The purpose of this pilot study was two-fold: to examine the relationship between developmental delays and dental caries in low-income preschoolers and to present a preliminary explanatory model on the determinants of caries for enrollees in Head Start, a U.S. school readiness program for low-income preschool-aged children. Methods Data were collected on preschoolers ages 3–5 years at two Head Start centers in Washington, USA (N = 115). The predictor variable was developmental delay status (no/yes). The outcome variable was the prevalence of decayed, missing, and filled surfaces (dmfs) on primary teeth. We used multiple variable Poisson regression models to test the hypothesis that within a population of low-income preschoolers, those with developmental delays would have increased dmfs prevalence than those without developmental delays. Results Seventeen percent of preschoolers had a developmental delay and 51.3% of preschoolers had ≥1 dmfs. Preschoolers with developmental delays had a dmfs prevalence ratio that was 1.26 times as high as preschoolers without developmental delays (95% CI: 1.01, 1.58; P < .04). Other factors associated with increased dmfs prevalence ratios included: not having a dental home (P = .01); low caregiver education (P < .001); and living in a non-fluoridated community (P < .001). Conclusions Our pilot data suggest that developmental delays among low-income preschoolers are associated with increased primary tooth dmfs. Additional research is needed to further examine this relationship. Future interventions and policies should focus on caries prevention strategies within settings like Head Start classrooms that serve low-income preschool-aged children with additional targeted home- and community-based interventions for those with developmental delays. PMID:24119240

De novo mutations of the ATP6V1A gene cause developmental encephalopathy with epilepsy.

PubMed

Fassio, Anna; Esposito, Alessandro; Kato, Mitsuhiro; Saitsu, Hirotomo; Mei, Davide; Marini, Carla; Conti, Valerio; Nakashima, Mitsuko; Okamoto, Nobuhiko; Olmez Turker, Akgun; Albuz, Burcu; Semerci Gündüz, C Nur; Yanagihara, Keiko; Belmonte, Elisa; Maragliano, Luca; Ramsey, Keri; Balak, Chris; Siniard, Ashley; Narayanan, Vinodh; Ohba, Chihiro; Shiina, Masaaki; Ogata, Kazuhiro; Matsumoto, Naomichi; Benfenati, Fabio; Guerrini, Renzo

2018-06-01

V-type proton (H+) ATPase (v-ATPase) is a multi-subunit proton pump that regulates pH homeostasis in all eukaryotic cells; in neurons, v-ATPase plays additional and unique roles in synapse function. Through whole exome sequencing, we identified de novo heterozygous mutations (p.Pro27Arg, p.Asp100Tyr, p.Asp349Asn, p.Asp371Gly) in ATP6V1A, encoding the A subunit of v-ATPase, in four patients with developmental encephalopathy with epilepsy. Early manifestations, observed in all patients, were developmental delay and febrile seizures, evolving to encephalopathy with profound delay, hypotonic/dyskinetic quadriparesis and intractable multiple seizure types in two patients (p.Pro27Arg, p.Asp100Tyr), and to moderate delay with milder epilepsy in the other two (p.Asp349Asn, p.Asp371Gly). Modelling performed on the available prokaryotic and eukaryotic structures of v-ATPase predicted p.Pro27Arg to perturb subunit interaction, p.Asp100Tyr to cause steric hindrance and destabilize protein folding, p.Asp349Asn to affect the catalytic function and p.Asp371Gly to impair the rotation process, necessary for proton transport. We addressed the impact of p.Asp349Asn and p.Asp100Tyr mutations on ATP6V1A expression and function by analysing ATP6V1A-overexpressing HEK293T cells and patients' lymphoblasts. The p.Asp100Tyr mutant was characterized by reduced expression due to increased degradation. Conversely, no decrease in expression and clearance was observed for p.Asp349Asn. In HEK293T cells overexpressing either pathogenic or control variants, p.Asp349Asn significantly increased LysoTracker® fluorescence with no effects on EEA1 and LAMP1 expression. Conversely, p.Asp100Tyr decreased both LysoTracker® fluorescence and LAMP1 levels, leaving EEA1 expression unaffected. Both mutations decreased v-ATPase recruitment to autophagosomes, with no major impact on autophagy. Experiments performed on patients' lymphoblasts using the LysoSensor™ probe revealed lower pH of endocytic organelles for p.Asp349Asn and a reduced expression of LAMP1 with no effect on the pH for p.Asp100Tyr. These data demonstrate gain of function for p.Asp349Asn characterized by an increased proton pumping in intracellular organelles, and loss of function for p.Asp100Tyr with decreased expression of ATP6V1A and reduced levels of lysosomal markers. We expressed p.Asp349Asn and p.Asp100Tyr in rat hippocampal neurons and confirmed significant and opposite effects in lysosomal labelling. However, both mutations caused a similar defect in neurite elongation accompanied by loss of excitatory inputs, revealing that altered lysosomal homeostasis markedly affects neurite development and synaptic connectivity. This study provides evidence that de novo heterozygous ATP6V1A mutations cause a developmental encephalopathy with a pathomechanism that involves perturbations of lysosomal homeostasis and neuronal connectivity, uncovering a novel role for v-ATPase in neuronal development.

Neonatal morbidities and developmental delay in moderately preterm-born children.

PubMed

Kerstjens, Jorien M; Bocca-Tjeertes, Inger F; de Winter, Andrea F; Reijneveld, Sijmen A; Bos, Arend F

2012-08-01

Children born moderately preterm (32-35(6/7) weeks' gestation) are at increased risk of both neonatal morbidities and developmental delays in early childhood. It is unknown whether neonatal morbidities contribute to the increased risk of developmental delay. The objective of this study was to determine the effect of neonatal morbidities after moderately preterm birth on development at preschool age. In a community-based, stratified cohort, parents of 832 moderately preterm children born in 2002 or 2003 completed the Ages and Stage Questionnaire when their child was 43 to 49 months old. Data on Apgar scores, asphyxia, tertiary NICU admission, hospital transfer, circulatory insufficiency, hypoglycemia, septicemia, mechanical ventilation, continuous positive airway pressure, apneas, caffeine treatment, and hyperbilirubinemia were obtained from medical records. We assessed associations of neonatal characteristics with developmental delay, adjusted for gender, small-for-gestational-age status, gestational age, and maternal education. Hypoglycemia and asphyxia were associated with developmental delay; odds ratios (ORs) were 2.42 (95% confidence interval [CI]: 1.23-4.77) and 3.18 (95% CI: 1.01-10.0), respectively. Tertiary NICU admission and hyperbilirubinemia had positive but statistically borderline nonsignificant associations with developmental delay: ORs were 1.74 (95% CI: 0.96-3.15) and 1.52 (95% CI: 0.94-2.46), respectively. No other neonatal morbidities were associated with developmental delay. In multivariate analyses, only hypoglycemia was associated with developmental delay (OR: 2.19; 95% CI: 1.08-4.46). In moderately preterm-born children, only hypoglycemia increased the risk of developmental delay at preschool age. A concerted effort to prevent hypoglycemia might enhance developmental outcome in this group.

[Clinical and genetic characteristics of children with Leigh syndrome].

PubMed

Fang, F; Shen, Y; Shen, D M; Liu, Z M; Ding, C H; Zhang, W C; Sun, S Z; Lyu, J L; Han, T L; Wang, X H; Zhang, W H; Yang, X Y; Li, J W; Wu, H S

2017-03-02

Objective: To investigate the clinically and genetic characteristics of children with Leigh syndrome. Method: Patients with clinically diagnosed Leigh syndrome(LS)in the department of Neurology, Beijing Children's Hospital from January 2013 to February 2016 underwent the mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) detecting with next generation sequencing (NGS) technology. The clinical data of gene confirmed cases were retrospectively collected and analyzed. The differences in the onset age, clinical manifestations, lactic acid level and MRI results between the mtDNA variation and nDNA variation were compared and analyzed. t test, Chi-square test and Fisher's exact test were used for statistical analysis. Result: Thirty-five cases were diagnosed by gene detection, including 20 males and 15 females. The median onset age was 1 year (ranging from the neonatal period to 4.4 years old). The age of onset within 2 years accounted for 74%(26 cases). The onset age of initial symptoms, including developmental delay, developmental regression, and seizures, were 6 (4, 12) months, 12 (8, 14) months, and 6 (1, 23) months respectively. The onset age of ptosis, extrapyramidal symptoms and ataxia were 26 (18, 44) months, 28 (23, 40) months and 28 (19, 35) months, respectively. There were significant differences in the onset age between the three groups ( H =21.919, P =0.01). Within the 35 cases, 29 were manifested with developmental delay (83%), 26 with dystonia (74%), 18 with growth retardation, 15 with myasthenia, 13 with developmental regression, 11 with dysphagia, 10 with feeding difficulties, 4 with skeletal dysplasia, and 2 with digestive tract symptoms; nystagmus and respiratory abnormalities were observed in 9 cases respectively; extrapyramidal symptoms, peripheral nerve injury, ptosis, seizures were observed in 8 cases respectively; and ataxia, ophthalmoplegia and hypertrichiasis were found in 5 cases respectively.The blood lactic acid was measured in 32 LS patients, within which 23 cases (72%) had increased results; 8 out of 11 cases who underwent were cerebrospinal fluid lactic acid test had increased results. The results of neuroimaging revealed that all the patients were involved in the brainstem and (or) basal ganglia, of whom 27 (77%) had brainstem involvement, 24 (69%) had basal ganglia involvement. Thirteen out of 14 patients who had medulla oblongata involvement had nDNA variation; while 7 out of 8 patients with cerebellar involvement had nDNA variation. Genetic etiology was confirmed in all patients, among whom there were 17 cases (49%) with mtDNA mutation, including 8993T>C/G ( n =5), 14487T>C ( n =4), 13513G>A ( n =2), 9176T>C, 10158T>C, 3697G>A, 10191T>C, 14459A>G and 11777C>A ( n =1) respectively. Remaining 18 cases(51%) had nDNA mutation, including SURF1 gene( n =10), PDHA1 gene( n =3) and one case each of NDUFV1, NDUFAF6, NDUFAF5, NDUFS1 and COQ7 genes. In this study, 27 types of mutations were founded, 15 of which had not been previously reported. Respiratory chain gene mutations have been found in 31 cases(89%); 3 cases had PDHc gene mutations, and 1 case had other mutation. Conclusion: LS usually occurs in infants. The most common primary symptoms are age-dependent abnormal movements, ocular symptoms, and seizures. Respiratory chain defects is the most common causes of LS.SURF1 is the most common variation, followed by 8993T>C/G, 14487 T>C and 13513G>A mutation.

Creatine Deficiency Syndrome could be Missed Easily: A Case Report of Guanidinoacetate Methyltransferase Deficiency Presented with Neurodevelopmental Delay, Seizures, and Behavioral Changes, but Normal Structural MRI.

PubMed

Pacheva, Iliyana; Ivanov, Ivan; Penkov, Marin; Kancheva, Daliya; Jordanova, Albena; Ivanova, Mariya

2016-09-01

A case with GAMT deficiency (homozygous c.64dupG mutation) presented with neurodevelopmental delay, rare seizures, behavioral disturbances, and mild hypotonia, posing diagnostic challenges. Metabolic investigations showed low creatinine in plasma and urine (guanidinoacetate couldn't be investigated) and slightly elevated lactate. MRI was normal. Correct diagnosis was possible only after MR spectroscopy was performed at age 5½ years. A homozygous c.64dupG mutation of the GAMT gene was identified in the proband. In conclusion, every case with neurodevelopmental delay or arrest, especially when accompanied by seizures, behavioral impairment, muscle hypotonia or extrapyramidal symptoms should undergo MRI with MR spectroscopy. Normal structural MRI doesn't exclude a creatine deficiency syndrome. Biochemical investigations of guanidinoacetate, creatine, and creatinine in body fluid should be done to diagnose cerebral creatine deficiency syndromes and to specify the deficient enzyme. Thus, a treatable disease will not be missed. © 2016 by the Association of Clinical Scientists, Inc.

Expanding the spectrum of phenotypes associated with germline PIGA mutations: a child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities.

PubMed

van der Crabben, Saskia N; Harakalova, Magdalena; Brilstra, Eva H; van Berkestijn, Frédérique M C; Hofstede, Floris C; van Vught, Adrianus J; Cuppen, Edwin; Kloosterman, Wigard; Ploos van Amstel, Hans Kristian; van Haaften, Gijs; van Haelst, Mieke M

2014-01-01

Phosphatidyl inositol glycan (PIG) enzyme subclasses are involved in distinct steps of glycosyl phosphatidyl inositol anchor protein biosynthesis. Glycolsyl phosphatidyl inositol-anchored proteins have heterogeneous functions; they can function as enzymes, adhesion molecules, complement regulators and co-receptors in signal transduction pathways. Germline mutations in genes encoding different members of the PIG family result in diverse conditions with (severe) developmental delay, (neonatal) seizures, hypotonia, CNS abnormalities, growth abnormalities, and congenital abnormalities as hallmark features. The variability of clinical features resembles the typical diversity of other glycosylation pathway deficiencies such as the congenital disorders of glycosylation. Here, we report the first germline missense mutation in the PIGA gene associated with accelerated linear growth, obesity, central hypotonia, severe refractory epilepsy, cardiac anomalies, mild facial dysmorphic features, mildly elevated alkaline phosphatase levels, and CNS anomalies consisting of progressive cerebral atrophy, insufficient myelinization, and cortical MRI signal abnormalities. X-exome sequencing in the proband identified a c.278C>T (p.Pro93Leu) mutation in the PIGA gene. The mother and maternal grandmother were unaffected carriers and the mother showed 100% skewing of the X-chromosome harboring the mutation. These results together with the clinical similarity of the patient reported here and the previously reported patients with a germline nonsense mutation in PIGA support the determination that this mutation caused the phenotype in this family. © 2013 Wiley Periodicals, Inc.

Global Developmental Delay and Its Relationship to Cognitive Skills

ERIC Educational Resources Information Center

Riou, Emilie M.; Ghosh, Shuvo; Francoeur, Emmett; Shevell, Michael I.

2009-01-01

Global developmental delay (GDD) is defined as evidence of significant delays in two or more developmental domains. Our study determined the cognitive skills of a cohort of young children with GDD. A retrospective chart review of all children diagnosed with GDD within a single developmental clinic was carried out. Scores on fine motor (Peabody…

[Neuropsychomotor developmental delay: conceptual map, term definitions, uses and limitations].

PubMed

Dornelas, Lílian de Fátima; Duarte, Neuza Maria de Castro; Magalhães, Lívia de Castro

2015-01-01

To retrieve the origin of the term neuropsychomotor developmental delay" (NPMD), its conceptual evolution over time, and to build a conceptual map based on literature review. A literature search was performed in the SciELO Brazil, Web of Science, Science Direct, OneFile (GALE), Pubmed (Medline), Whiley Online, and Springer databases, from January of 1940 to January of 2013, using the following keywords NPMD delay, NPMD retardation, developmental delay, and global developmental delay. A total of 71 articles were selected, which were used to build the conceptual map of the term. Of the 71 references, 55 were international and 16 national. The terms developmental delay and global developmental delay were the most frequently used in the international literature and, in Brazil, delayed NPMD was the most often used. The term developmental delay emerged in the mid 1940s, gaining momentum in the 1990 s. In Brazil, the term delayed NPMD started to be used in the 1980s, and has been frequently cited and published in the literature. Delayed development was a characteristic of 13 morbidities described in 23 references. Regarding the type of use, 19 references were found, with seven forms of use. Among the references, 34 had definitions of the term, and 16 different concepts were identified. Developmental delay is addressed in the international and national literature under different names, various applications, and heterogeneous concepts. Internationally, ways to improve communication between professionals have been indicated, with standardized definition of the term and use in very specific situations up to the fifth year of life, which was not found in Brazilian publications. Copyright © 2014 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Neuropsychomotor developmental delay: conceptual map, term definitions, uses and limitations

PubMed Central

Dornelas, Lílian de Fátima; Duarte, Neuza Maria de Castro; Magalhães, Lívia de Castro

2015-01-01

OBJECTIVE: To retrieve the origin of the term neuropsychomotor developmental delay" (NPMD), its conceptual evolution over time, and to build a conceptual map based on literature review. DATA SOURCE: A literature search was performed in the SciELO Brazil, Web of Science, Science Direct, OneFile (GALE), Pubmed (Medline), Whiley Online, and Springer databases, from January of 1940 to January of 2013, using the following keywords: NPMD delay, NPMD retardation, developmental delay, and global developmental delay. A total of 71 articles were selected, which were used to build the conceptual map of the term. DATA SYNTHESIS: Of the 71 references, 55 were international and 16 national. The terms developmental delay and global developmental delay were the most frequently used in the international literature and, in Brazil, delayed NPMD was the most often used. The term developmental delay emerged in the mid 1940s, gaining momentum in the 1990s. In Brazil, the term delayed NPMD started to be used in the 1980s, and has been frequently cited and published in the literature. Delayed development was a characteristic of 13 morbidities described in 23 references. Regarding the type of use, 19 references were found, with seven forms of use. Among the references, 34 had definitions of the term, and 16 different concepts were identified. CONCLUSIONS: Developmental delay is addressed in the international and national literature under different names, various applications, and heterogeneous concepts. Internationally, ways to improve communication between professionals have been indicated, with standardized definition of the term and use in very specific situations up to the fifth year of life, which was not found in Brazilian publications. PMID:25662016

Profile of referrals for early childhood developmental delay to ambulatory subspecialty clinics.

PubMed

Shevell, M I; Majnemer, A; Rosenbaum, P; Abrahamowicz, M

2001-09-01

The objective of this study was to determine the profile and pattern of referral to subspecialty clinics of young children with suspected developmental delay together with the factors prompting their referral. All children under 5 years of age referred to either developmental pediatrics or pediatric neurology clinics at a single tertiary hospital over an 18-month period were prospectively identified. Standardized demographic and referral information were collected at intake, final developmental delay subtype diagnosed was identified, and referring physicians were surveyed regarding factors prompting referral. A total of 224 children met study criteria. There was a marked male preponderance (166/224), especially among those with either cognitive or language delay. Two delay subtypes, global developmental delay and developmental language disorder, accounted for two thirds of the diagnoses made. For slightly more than one third of the children (75/224), the delay subtype diagnosed following specialty evaluation was different from that initially suspected by the referring physician. A mean delay of 15.5 months was observed for the cohort as a whole between initial parental concern and specialty assessment. For referring physicians, the major factor prompting referral was the severity of the observed delay. The most important aspects of the specialty evaluation according to referral sources were the identification of a possible etiology and confirmation of delay. A profile of referrals and the rationale thereof for a cohort of children with suspected developmental delay is presented that, although locale specific, has implications for service provision and training.

Occipitoparietal epilepsy, hippocampal atrophy, and congenital developmental abnormalities.

PubMed

Lawn, N; Londono, A; Sawrie, S; Morawetz, R; Martin, R; Gilliam, F; Faught, E; Kuzniecky, R

2000-12-01

Diagnostic uncertainty may arise in patients with occipitoparietal epilepsy when there is neuroimaging evidence of a posterior quadrant lesion and coexistent hippocampal abnormalities ("dual pathology"). It is not known whether hippocampal atrophy (HA) in these patients results from seizure propagation to temporolimbic structures or whether it is part of the pathological process underlying the occipitoparietal epilepsy. Clarification of this issue may have a significant bearing on the management of these patients. We studied 20 patients with occipitoparietal epilepsy and neuroimaging or pathologic evidence of a congenital developmental abnormality. Normalized hippocampal volumes were obtained in all patients. The medical records and video-EEG recordings were analyzed to correlate the MRI findings with clinical data, seizure semiology, and EEG findings. HA was found in seven patients (35%). Neuroimaging abnormalities concordant with the side of HA were seen in all cases. There was clinical or EEG evidence of temporal spread in 12 patients. There was no correlation between the presence of HA and temporal lobe spread. The only clinical factor associated with HA in this series was a younger age of seizure onset. HA in patients with occipitoparietal epilepsy due to congenital developmental abnormalities is most likely to be a marker of a more widespread process related to a common pathogenesis during prenatal or perinatal development. HA in these patients is unlikely to be the result of secondary spread from an extrahippocampal focus. Surgical treatment should be tailored toward the primary epileptogenic zone rather the site of seizure spread.

Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target?

PubMed

Horvath, Gabriella A; Demos, Michelle; Shyr, Casper; Matthews, Allison; Zhang, Linhua; Race, Simone; Stockler-Ipsiroglu, Sylvia; Van Allen, Margot I; Mancarci, Ogan; Toker, Lilah; Pavlidis, Paul; Ross, Colin J; Wasserman, Wyeth W; Trump, Natalie; Heales, Simon; Pope, Simon; Cross, J Helen; van Karnebeek, Clara D M

2016-01-01

We describe neurotransmitter abnormalities in two patients with drug-resistant epilepsy resulting from deleterious de novo mutations in sodium channel genes. Whole exome sequencing identified a de novo SCN2A splice-site mutation (c.2379+1G>A, p.Glu717Gly.fs*30) resulting in deletion of exon 14, in a 10-year old male with early onset global developmental delay, intermittent ataxia, autism, hypotonia, epileptic encephalopathy and cerebral/cerebellar atrophy. In the cerebrospinal fluid both homovanillic acid and 5-hydroxyindoleacetic acid were significantly decreased; extensive biochemical and genetic investigations ruled out primary neurotransmitter deficiencies and other known inborn errors of metabolism. In an 8-year old female with an early onset intractable epileptic encephalopathy, developmental regression, and progressive cerebellar atrophy, a previously unreported de novo missense mutation was identified in SCN8A (c.5615G>A; p.Arg1872Gln), affecting a highly conserved residue located in the C-terminal of the Nav1.6 protein. Aside from decreased homovanillic acid and 5-hydroxyindoleacetic acid, 5-methyltetrahydrofolate was also found to be low. We hypothesize that these channelopathies cause abnormal synaptic mono-amine metabolite secretion/uptake via impaired vesicular release and imbalance in electrochemical ion gradients, which in turn aggravate the seizures. Treatment with oral 5-hydroxytryptophan, l-Dopa/Carbidopa, and a dopa agonist resulted in mild improvement of seizure control in the male case, most likely via dopamine and serotonin receptor activated signal transduction and modulation of glutamatergic, GABA-ergic and glycinergic neurotransmission. Neurotransmitter analysis in other sodium channelopathy patients will help validate our findings, potentially yielding novel treatment opportunities. Copyright © 2015 Elsevier Inc. All rights reserved.

Association of Arsenic Methylation Capacity with Developmental Delays and Health Status in Children: A Prospective Case-Control Trial

NASA Astrophysics Data System (ADS)

Hsueh, Yu-Mei; Chen, Wei-Jen; Lee, Chih-Ying; Chien, Ssu-Ning; Shiue, Horng-Sheng; Huang, Shiau-Rung; Lin, Ming-I.; Mu, Shu-Chi; Hsieh, Ru-Lan

2016-11-01

This case-control study identified the association between the arsenic methylation capacity and developmental delays and explored the association of this capacity with the health status of children. We recruited 120 children with developmental delays and 120 age- and sex-matched children without developmental delays. The health status of the children was assessed using the Pediatric Quality of Life Inventory (PedsQL) and Pediatric Outcomes Data Collection Instrument (PODCI). The arsenic methylation capacity was determined by the percentages of inorganic arsenic (InAs%), monomethylarsonic acid (MMAV%), and dimethylarsinic acid (DMAV%) through liquid chromatography and hydride generation atomic absorption spectrometry. Developmental delays were significantly positively associated with the total urinary arsenic concentration, InAs%, and MMAV%, and was significantly negatively associated with DMAV% in a dose-dependent manner. MMAV% was negatively associated with the health-related quality of life (HRQOL; -1.19 to -1.46, P < 0.01) and functional performance (-0.82 to -1.14, P < 0.01), whereas DMAV% was positively associated with HRQOL (0.33-0.35, P < 0.05) and functional performance (0.21-0.39, P < 0.01-0.05) in all children and in those with developmental delays. The arsenic methylation capacity is dose-dependently associated with developmental delays and with the health status of children, particularly those with developmental delays.

Young Children with Developmental Delays as Young Adults: Predicting Developmental and Personal-Social Outcomes

ERIC Educational Resources Information Center

Bernheimer, Lucinda P.; Keogh, Barbara K.; Guthrie, Donald

2006-01-01

We report on a 20-year follow-up of 30 children with developmental delays identified at age 3. Our purpose was to assess the relationship of early indicators of delay to cognitive and personal-social status in young adulthood. Predictors were Developmental and Personal-Social factors derived from standardized tests and parent questionnaires…

The effects of early-life seizures on hippocampal dendrite development and later-life learning and memory.

PubMed

Casanova, J R; Nishimura, Masataka; Swann, John W

2014-04-01

Severe childhood epilepsy is commonly associated with intellectual developmental disabilities. The reasons for these cognitive deficits are likely multifactorial and will vary between epilepsy syndromes and even among children with the same syndrome. However, one factor these children have in common is the recurring seizures they experience - sometimes on a daily basis. Supporting the idea that the seizures themselves can contribute to intellectual disabilities are laboratory results demonstrating spatial learning and memory deficits in normal mice and rats that have experienced recurrent seizures in infancy. Studies reviewed here have shown that seizures in vivo and electrographic seizure activity in vitro both suppress the growth of hippocampal pyramidal cell dendrites. A simplification of dendritic arborization and a resulting decrease in the number and/or properties of the excitatory synapses on them could help explain the observed cognitive disabilities. There are a wide variety of candidate mechanisms that could be involved in seizure-induced growth suppression. The challenge is designing experiments that will help focus research on a limited number of potential molecular events. Thus far, results suggest that growth suppression is NMDA receptor-dependent and associated with a decrease in activation of the transcription factor CREB. The latter result is intriguing since CREB is known to play an important role in dendrite growth. Seizure-induced dendrite growth suppression may not occur as a single process in which pyramidal cells dendrites simply stop growing or grow slower compared to normal neurons. Instead, recent results suggest that after only a few hours of synchronized epileptiform activity in vitro dendrites appear to partially retract. This acute response is also NMDA receptor dependent and appears to be mediated by the Ca(+2)/calmodulin-dependent phosphatase, calcineurin. An understanding of the staging of seizure-induced growth suppression and the underlying molecular mechanisms will likely prove crucial for developing therapeutic strategies aimed at ameliorating the intellectual developmental disabilities associated with intractable childhood epilepsy. Copyright © 2013 Elsevier Inc. All rights reserved.

Age-dependent effects of topiramate on the acquisition and the retention of rapid kindling.

PubMed

Mazarati, Andréy; Shin, Don; Auvin, Stéphane; Sankar, Raman

2007-04-01

To examine antiepileptogenic, disease modifying, and anticonvulsant effects of topiramate under conditions of rapid kindling at different stages of development. Afterdischarge threshold (ADT) and duration (ADD) were examined in 2-, 3-, and 5-week-old Wistar rats before and after administration of topiramate (200 mg/kg). Animals underwent a rapid kindling protocol (sixty 10-s trains, bipolar 20 Hz square wave pulses delivered every 5 min). The progression of behavioral and electrographic seizures, and responses to test stimulations 24 h after the protocol were compared between topiramate and vehicle-treated control rats. In addition, rats that were previously given vehicle only prior to kindling, were then given topiramate to examine the effect on established kindled seizures. In 2-week-old animals, topiramate affected neither the baseline afterdischarge, nor the progression of kindled seizures. In 3-week-old rats, topiramate did not modify the baseline afterdischarge, but significantly delayed the occurrence of full motor seizures in response to repeated stimulations. Topiramate treatment of 5-week-old rats increased baseline ADT, shortened ADD, and delayed the progression of kindled seizures. Twenty-four h after the last kindling stimulation, animals of all ages exhibited a decreased ADT, an increase ADD, and developed behavioral seizures in response to threshold stimulation. Vehicle-treated kindled rats that were then given topiramate displayed significantly attenuated behavioral seizures induced by the threshold stimulation. Topiramate exhibited age-dependent disease-modifying effects under conditions of rapid kindling, but failed to block epileptogenesis. Topiramate also inhibited kindled seizures with equal efficacy across the three ages.

Age-Dependent Effects of Topiramate on the Acquisition and the Retention of Rapid Kindling

PubMed Central

Mazarati, Andréy; Shin, Don; Auvin, Stéphane; Sankar, Raman

2008-01-01

Summary Purpose To examine antiepileptogenic, disease-modifying, and anticonvulsant effects of topiramate under conditions of rapid kindling at different stages of development. Methods Afterdischarge threshold (ADT) and duration (ADD) were examined in two-, three-, and five-week old Wistar rats before and after administration of topiramate (200 mg/kg). Animals underwent a rapid kindling protocol (sixty 10 second trains, bipolar 20 Hz square wave pulses delivered every five minutes). The progression of behavioral and electrographic seizures, and responses to test stimulations 24 hours after the protocol were compared between topiramate and vehicle treated control rats. In addition, rats that were previously given vehicle only prior to kindling, were then given topiramate to examine the effect on established kindled seizures. Results In two-week old animals, topiramate affected neither the baseline afterdischarge, nor the progression of kindled seizures. In three-week old rats, topiramate did not modify the baseline afterdischarge, but significantly delayed the occurrence of full motor seizures in response to repeated stimulations. Topiramate treatment of five-week old rats increased baseline ADT, shortened ADD, and delayed the progression of kindled seizures. Twenty four hours after the last kindling stimulation, animals of all ages exhibited a decreased ADT, an increase ADD, and developed behavioral seizures in response to threshold stimulation. Vehicle treated kindled rats that were then given topiramate displayed significantly attenuated behavioral seizures induced by the threshold stimulation. Conclusions Topiramate exhibited age-dependent disease-modifying effects under conditions of rapid kindling, but failed to block epileptogenesis. Topiramate also inhibited kindled seizures with equal efficacy across the three ages. PMID:17319916

A hierarchical approach for online temporal lobe seizure detection in long-term intracranial EEG recordings

NASA Astrophysics Data System (ADS)

Liang, Sheng-Fu; Chen, Yi-Chun; Wang, Yu-Lin; Chen, Pin-Tzu; Yang, Chia-Hsiang; Chiueh, Herming

2013-08-01

Objective. Around 1% of the world's population is affected by epilepsy, and nearly 25% of patients cannot be treated effectively by available therapies. The presence of closed-loop seizure-triggered stimulation provides a promising solution for these patients. Realization of fast, accurate, and energy-efficient seizure detection is the key to such implants. In this study, we propose a two-stage on-line seizure detection algorithm with low-energy consumption for temporal lobe epilepsy (TLE). Approach. Multi-channel signals are processed through independent component analysis and the most representative independent component (IC) is automatically selected to eliminate artifacts. Seizure-like intracranial electroencephalogram (iEEG) segments are fast detected in the first stage of the proposed method and these seizures are confirmed in the second stage. The conditional activation of the second-stage signal processing reduces the computational effort, and hence energy, since most of the non-seizure events are filtered out in the first stage. Main results. Long-term iEEG recordings of 11 patients who suffered from TLE were analyzed via leave-one-out cross validation. The proposed method has a detection accuracy of 95.24%, a false alarm rate of 0.09/h, and an average detection delay time of 9.2 s. For the six patients with mesial TLE, a detection accuracy of 100.0%, a false alarm rate of 0.06/h, and an average detection delay time of 4.8 s can be achieved. The hierarchical approach provides a 90% energy reduction, yielding effective and energy-efficient implementation for real-time epileptic seizure detection. Significance. An on-line seizure detection method that can be applied to monitor continuous iEEG signals of patients who suffered from TLE was developed. An IC selection strategy to automatically determine the most seizure-related IC for seizure detection was also proposed. The system has advantages of (1) high detection accuracy, (2) low false alarm, (3) short detection latency, and (4) energy-efficient design for hardware implementation.

Global developmental delay in guanidionacetate methyltransferase deficiency: differences in formal testing and clinical observation.

PubMed

Verbruggen, Krijn T; Knijff, Wilma A; Soorani-Lunsing, Roelineke J; Sijens, Paul E; Verhoeven, Nanda M; Salomons, Gajja S; Goorhuis-Brouwer, Siena M; van Spronsen, Francjan J

2007-09-01

Guanidinoacetate N-methyltransferase (GAMT) deficiency is a defect in the biosynthesis of creatine (Cr). So far, reports have not focused on the description of developmental abilities in this disorder. Here, we present the result of formal testing of developmental abilities in a GAMT-deficient patient. Our patient, a 3-year-old boy with GAMT deficiency, presented clinically with a severe language production delay and nearly normal nonverbal development. Treatment with oral Cr supplementation led to partial restoration of the cerebral Cr concentration and a clinically remarkable acceleration of language production development. In contrast to clinical observation, formal testing showed a rather harmonic developmental delay before therapy and a general improvement, but no specific acceleration of language development after therapy. From our case, we conclude that in GAMT deficiency language delay is not always more prominent than delays in other developmental areas. The discrepancy between the clinical impression and formal testing underscores the importance of applying standardized tests in children with developmental delays. Screening for Cr deficiency by metabolite analysis of body fluids or proton magnetic resonance spectroscopy of the brain deficiency should be considered in any child with global developmental delay/mental retardation lacking clues for an alternative etiology.

Maternal nationality and developmental delays in young children: Analysis of the data from the national registry in Taiwan.

PubMed

Tseng, Yen-Cheng; Guo, How-Ran; Lai, Der-Chung

2016-01-01

With globalization, transnational marriages become more and more common around the world. Children born to immigrant mothers might be more likely to have developmental delays, but studies on this topic are limited and with inconsistent results. To determine whether children born to immigrant mothers are more likely to have developmental delays. We analyzed the data from the national registry of children with developmental delays from 2009 to 2013 and compared the incidence of developmental delays between children born to immigrant mothers and native mothers. We also performed stratified analyses by age, sex, and geographic area. From 2009 to 2013, 78,946 new cases of developmental delays under 6 years of age were registered, including 5619 (7.1%) born to immigrant mothers. The incidence was higher in children born to native mothers in every year with rate ratios ranging from 1.32 to 1.48, and the differences reached statistical significance even after stratification by age, sex, and geographic area. Children born to immigrant mothers had lower incidence of developmental delays in Taiwan. The result may help reduce the discrimination of foreign spouses and their children. Copyright © 2016 Elsevier Ltd. All rights reserved.

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy.

PubMed

Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John

2013-03-01

The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant.

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy

PubMed Central

Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John

2013-01-01

The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant. PMID:22872100

Interference of TRPV1 function altered the susceptibility of PTZ-induced seizures.

PubMed

Jia, Yun-Fang; Li, Ying-Chao; Tang, Yan-Ping; Cao, Jun; Wang, Li-Ping; Yang, Yue-Xiong; Xu, Lin; Mao, Rong-Rong

2015-01-01

Transient receptor potential vanilloid 1 (TRPV1) is widely distributed in the central nervous system (CNS) including hippocampus, and regulates the balance of excitation and inhibition in CNS, which imply its important role in epilepsy. We used both pharmacological manipulations and transgenic mice to disturb the function of TRPV1 and then studied the effects of these alterations on the susceptibility of pentylenetetrazol (PTZ)-induced seizures. Our results showed that systemic administration of TRPV1 agonist capsaicin (CAP, 40 mg/kg) directly induced tonic-clonic seizures (TCS) without PTZ induction. The severity of seizure was increased in lower doses of CAP groups (5 and 10 mg/kg), although the latency to TCS was delayed. On the other hand, systemic administration of TRPV1 antagonist capsazepine (CPZ, 0.05 and 0.5 mg/kg) and TRPV1 knockout mice exhibited delayed latency to TCS and reduced mortality. Furthermore, hippocampal administration of CPZ (10 and 33 nmol/μL/side) was firstly reported to increase the latency to TCS, decrease the maximal grade of seizure and mortality. It is worth noting that decreased susceptibility of PTZ-induced seizures was observed in hippocampal TRPV1 overexpression mice and hippocampal CAP administration (33 nmol/μL/side), which is opposite from results of systemic agonist CAP. Our findings suggest that the systemic administration of TRPV1 antagonist may be a novel therapeutic target for epilepsy, and alteration of hippocampal TRPV1 function exerts a critical role in seizure susceptibility.

The administrative population report on children with developmental delays in Taiwan, 2003 through 2007.

PubMed

Lin, Jin-Ding; Yen, Chia-Feng; Wu, Jia-Ling; Kang, Shih-Wan

2009-01-01

This paper was a population study with developmental delays and it included an examination of the trends the overtime change trend and reported channels of this group of people in Taiwan. We analyzed data for the present study mainly from the Department of Statistics, Ministry of the Interiors, Taipei, Taiwan: "Number of early intervention for children with developmental delays in Taiwan" from 2003 through 2007. The reported number of children with developmental delays slightly increased from 13,231 to 14,250 (increase rate=7.7%) from the year of 2003 through 2007 in Taiwan. More than one-half of children with developmental delays were reported during the age 3-5 years. Aged 0-2 group has the highest increasing reported numbers in the previous 5 years which changed dramatically increased from 4139 (31.3%) in 2003 to 6201 (43.5%) in 2007 (increase rate=49.8%). The medical care setting was the main reported channel of the children with developmental delays and the results also showed that the reported prevalence of the aged 0-2 developmentally delayed children was 57.4-102.2 per 10,000 children; aged 3-5 was 79.0-105.1 per 10,000 children from the year 2003-2007 in Taiwan. The present concluded that early intervention based on the precise affected population would provide important supports for families of children with developmental delays. Therefore, the health care system should be strengthened to increase the proportion of children identified at the earlier age and to decrease the variability in the age at identification for most of the conditions of children with developmental delays.

Creatine deficiency syndromes.

PubMed

Schulze, Andreas

2013-01-01

The lack of creatine in the central nervous system causes a severe but treatable neurological disease. Three inherited defects, AGAT, GAMT, and CrT deficiency, compromising synthesis and transport of creatine have been discovered recently. Together these so-called creatine deficiency syndromes (CDS) might represent the most frequent metabolic disorders with a primarily neurological phenotype. Patients with CDS present with global developmental delays, mental retardation, speech impairment especially affecting active language, seizures, extrapyramidal movement disorder, and autism spectrum disorder. The two defects in the creatine synthesis, AGAT and GAMT, are autosomal recessive disorders. They can be diagnosed by analysis of the creatine, guanidinoacetate, and creatinine in body fluids. Treatment is available and, especially when introduced in infancy, has a good outcome. The defect of creatine transport, CrT, is an X-linked condition and perhaps the most frequent reasons for X-linked mental retardation. Diagnosis is made by an increased ratio of creatine to creatinine in urine, but successful treatment still needs to be explored. CDS are under-diagnosed because easy to miss in standard diagnostic workup. Because CDS represent a frequent cause of cognitive and neurological impairment that is treatable they warrant consideration in the workup for genetic mental retardation syndromes, for intractable seizure disorders, and for neurological diseases with a predominant lack of active speech. Copyright © 2013 Elsevier B.V. All rights reserved.

The novel homozygous KCNJ10 c.986T>C (p.(Leu329Pro)) variant is pathogenic for the SeSAME/EAST homologue in Malinois dogs

PubMed Central

Van Poucke, Mario; Stee, Kimberley; Bhatti, Sofie F M; Vanhaesebrouck, An; Bosseler, Leslie; Peelman, Luc J; Van Ham, Luc

2017-01-01

SeSAME/EAST syndrome is a multisystemic disorder in humans, characterised by seizures, sensorineural deafness, ataxia, developmental delay and electrolyte imbalance. It is exclusively caused by homozygous or compound heterozygous variations in the KCNJ10 gene. Here we describe a similar syndrome in two families belonging to the Malinois dog breed, based on clinical, neurological, electrodiagnostic and histopathological examination. Genetic analysis detected a novel pathogenic KCNJ10 c.986T>C (p.(Leu329Pro)) variant that is inherited in an autosomal recessive way. This variant has an allele frequency of 2.9% in the Belgian Malinois population, but is not found in closely related dog breeds or in dog breeds where similar symptoms have been already described. The canine phenotype is remarkably similar to humans, including ataxia and seizures. In addition, in half of the dogs clinical and electrophysiological signs of neuromyotonia were observed. Because there is currently no cure and treatment is nonspecific and unsatisfactory, this canine translational model could be used for further elucidating the genotype/phenotype correlation of this monogenic multisystem disorder and as an excellent intermediate step for drug safety testing and efficacy evaluations before initiating human studies. PMID:27966545

GLUT1 deficiency syndrome as a cause of encephalopathy that includes cognitive disability, treatment-resistant infantile epilepsy and a complex movement disorder.

PubMed

Graham, John M

2012-05-01

Glucose transporter-1 (GLUT1) deficiency syndrome is caused by heterozygous mutations in the SLC2A1 gene, resulting in impaired glucose transport into the brain. It is characterized by a low glucose concentration in the cerebrospinal fluid (hypoglycorrhachia) in the absence of hypoglycemia, in combination with low to normal lactate in the cerebrospinal fluid (CSF). It often results in treatment-resistant infantile epilepsy with progressive developmental disabilities and a complex movement disorder. Recognizing GLUT1 deficiency syndrome is important, since initiation of a ketogenic diet can reduce the frequency of seizures and the severity of the movement disorder. There can be a considerable delay in diagnosing GLUT1 deficiency syndrome, and this point is illustrated by the natural history of this disorder in a 21-year-old woman with severe, progressive neurological disabilities. Her encephalopathy consisted of treatment-resistant seizures, a complex movement disorder, progressive intellectual disability, and deceleration of her head growth after late infancy. Focused evaluation at age 21 revealed GLUT1 deficiency caused by a novel heterozygous missence mutation in exon 7 (c.938C > A; p.Ser313Try) in SLC2A1 as the cause for her disabilities. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

A clinical approach to developmental delay and intellectual disability.

PubMed

Vasudevan, Pradeep; Suri, Mohnish

2017-12-01

Global developmental delay and intellectual disability are phenotypically and genetically heterogeneous and a specific diagnosis is not reached in many cases. This paper outlines a systematic approach to global developmental delay and intellectual disability. © Royal College of Physicians 2017. All rights reserved.

Correlation Between Mothers' Depression and Developmental Delay in Infants Aged 6-18 Months.

PubMed

Vameghi, Roshanak; Amir Ali Akbari, Sedigheh; Sajjadi, Homeira; Sajedi, Firoozeh; Alavimajd, Hamid

2015-08-23

Regarding the importance of children's developmental status and various factors that delay their development, this study was conducted to examine the correlation between mothers' depression levels and the developmental delay in infants. This descriptive study was performed on 1053 mothers and their infants' age 6 to18 month-old in medical centers affiliated with Shahid Beheshti University of Medical Sciences, Iran, in 2014-2015. The participants were selected through multi-stage random sampling. The following instruments were used in this study: A demographic and obstetric specification questionnaire, infant specification questionnaire, the Beck Depression Inventory, and the Ages and Stages Questionnaire to determine the status of the children's development. The data were analyzed using SPSS19 software, Mann-Whitney; independent T-test and logistic-Regression tests were used. The results showed that 491 mothers (46.7%) suffered mild to extremely severe depression. The delay in infant development was 11.8%. The Mann-Whitney test showed a correlation between mothers' depression levels and developmental delay in infants (P=0.001). Moreover, there was a significant correlation between mothers' depression and developmental delays in gross-motor and problem-solving skills (P<0/05). In logistic model age of infants showed significant correlation with developmental delay (P=0.004 OR=1.07), but unwanted pregnancy, gender of infants, type of delivery and socioeconomic status had no correlation with developmental delay. Given the correlation between mothers' depression and infant development, it is recommended to screen mothers for depression in order to perform early interventions in developmental delay.

Cerebrotendinous xanthomatosis (CTX): an association of pulverulent cataracts and pseudo-dominant developmental delay in a family with a splice site mutation in CYP27A1--a case report.

PubMed

Bourkiza, Rabia; Joyce, Sarah; Patel, Himanshu; Chan, Michelle; Meyer, Esther; Maher, Eamonn R; Reddy, M Ashwin

2010-06-01

A 15-year-old boy with developmental delay presented to the pediatric ophthalmology clinic with bilateral pulverulent cataracts. The family was examined for developmental delay, cataracts and systemic problems. The parents were consanguineous and originally from Bangladesh. All the children were born in the UK. The mother and 5 children had developmental delay. Three children had global developmental delay, diarrhea and pulverulent cataracts. Two children had microcephaly, developmental delay, constipation and no cataracts. The mother did not have microcephaly, cataracts or gastrointestinal problems. Linkage analysis via autozygosity testing was performed for detection of loci and candidate genes. The patients with cataracts were segregated with homozygous mutations in the CYP27A1 (G to A substitution at position +1 of intron 6). The complex nature of this family's findings suggested that it had an unusual autosomal dominant condition with variable expression. Autozygosity testing demonstrated that three members had Cerebrotendinous xanthomatosis (CTX), which is inherited in an autosomal recessive manner. The aetiology of the developmental delay in other family members remains unknown. Cerebrotendinous xanthomatosis is a rare autosomal recessive condition that can result in neurological deficits and early death if left untreated. In view of the reversible nature of the condition with appropriate treatment, there needs to be a high level of suspicion of CTX for any child with cataracts and developmental delay even if the pattern of inheritance is not straightforward at initial assessment.

Relation of polymorphism of arsenic metabolism genes to arsenic methylation capacity and developmental delay in preschool children in Taiwan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsieh, Ru-Lan

Inefficient arsenic methylation capacity has been associated with developmental delay in children. The present study was designed to explore whether polymorphisms and haplotypes of arsenic methyltransferase (AS3MT), glutathione-S-transferase omegas (GSTOs), and purine nucleoside phosphorylase (PNP) affect arsenic methylation capacity and developmental delay. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 179 children with developmental delay and 88 children without delay were recruited. Urinary arsenic species, including arsenite (As{sup III}), arsenate (As{sup V}), monomethylarsonic acid (MMA{sup V}), and dimethylarsinic acid (DMA{sup V}) weremore » measured using a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphisms of AS3MT, GSTO, and PNP were performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Polymorphisms of AS3MT genes were found to affect susceptibility to developmental delay in children, but GSTO and PNP polymorphisms were not. Participants with AS3MT rs3740392 A/G + G/G genotype, compared with AS3MT rs3740392 A/A genotype, had a significantly lower secondary methylation index. This may result in an increased OR for developmental delay. Participants with the AS3MT high-risk haplotype had a significantly higher OR than those with AS3MT low-risk haplotypes [OR and 95% CI, 1.59 (1.08–2.34)]. This is the first study to show a joint dose-response effect of this AS3MT high-risk haplotype and inefficient arsenic methylation capacity on developmental delay. Our data provide evidence that AS3MT genes are related to developmental delay and may partially influence arsenic methylation capacity. - Highlights: • AS3MT genotypes were found to affect susceptibility to developmental delay. • AS3MT rs3740392 A/G and G/G genotype had a significantly low SMI (DMA/MMA) index. • AS3MT high-risk haplotype was significantly associated with developmental delay.« less

Antiepileptic effects of levetiracetam in a rodent neonatal seizure model.

PubMed

Talos, Delia M; Chang, Meayoung; Kosaras, Bela; Fitzgerald, Erin; Murphy, Andrew; Folkerth, Rebecca Dunn; Jensen, Frances E

2013-01-01

Neonatal seizures can result in chronic epilepsy and long-term behavioral and cognitive deficits. Levetiracetam (LEV), an antiepileptic drug that binds to the synaptic vesicle protein 2A (SV2A), has been increasingly used off-label for the therapy of neonatal seizures. Preclinical data regarding the acute or long-term efficacy of LEV are lacking. We tested the anticonvulsant efficacy of LEV in a rat model of hypoxia-induced neonatal seizures. In addition, we evaluated the protective effects of postnatal day (P)10 LEV treatment on later-life kainic acid (KA)-induced seizure susceptibility and seizure-induced neuronal injury. Western blot and immunohistochemistry were used to assess the developmental regulation of SV2A in the rat and human brain. LEV pretreatment at P10 significantly decreased the cumulative duration of behavioral and electrographic seizures at both 25 and 50 mg/kg. At P40, KA-induced seizures and neuronal loss were significantly diminished in rats previously treated with LEV. LEV target SV2A is present in both neonatal rat and human brain and increases steadily to adulthood. LEV suppressed acute seizures induced by perinatal hypoxia and diminished later-life seizure susceptibility and seizure-induced neuronal injury, providing evidence for disease modification. These results support consideration of a clinical trial of LEV in neonatal seizures.

Abnormal behavior in children with temporal lobe epilepsy and ganglioglioma.

PubMed

Guimarães, Catarina A; Franzon, Renata C; Souza, Elisabete A P; Schmutzler, Kátia M R S; Montenegro, Maria Augusta; Queiroz, Luciano de S; Cendes, Fernando; Guerreiro, Marilisa M

2004-10-01

Temporal lobe epilepsy in childhood is characterized by great clinical, electroencephalographic, and etiological diversity. The prognosis after temporal lobe epilepsy surgery in childhood is usually good, with most patients achieving complete seizure control. However, in some children behavior deteriorates postoperatively. We report two girls (2 and 6 years of age) with refractory seizures due to temporal lobe ganglioglioma. They exhibited aggression and hyperactivity since the beginning of their epilepsy. In both patients, behavioral disturbances worsened postoperatively, despite complete seizure control. Patients and parents should be advised about possible behavioral disturbances after epilepsy surgery, especially in the presence of a temporal lobe developmental tumor, even when seizure control is achieved postoperatively.

The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin.

PubMed

Barker, Bryan S; Ottolini, Matteo; Wagnon, Jacy L; Hollander, Rachel M; Meisler, Miriam H; Patel, Manoj K

2016-09-01

SCN8A encephalopathy (early infantile epileptic encephalopathy; EIEE13) is caused by gain-of-function mutations resulting in hyperactivity of the voltage-gated sodium channel Nav 1.6. The channel is concentrated at the axon initial segment (AIS) and is involved in establishing neuronal excitability. Clinical features of SCN8A encephalopathy include seizure onset between 0 and 18 months of age, intellectual disability, and developmental delay. Seizures are often refractory to treatment with standard antiepileptic drugs, and sudden unexpected death in epilepsy (SUDEP) has been reported in approximately 10% of patients. In a recent study, high doses of phenytoin were effective in four patients with SCN8A encephalopathy. In view of this observation, we have investigated the relationship between the functional effect of the SCN8A mutation p.Ile1327Val and its response to phenytoin. The mutation was introduced into the Scn8a cDNA by site-directed mutagenesis. Channel activity was characterized in transfected ND7/23 cells. The effects of phenytoin (100 μm) on mutant and wild-type (WT) channels were compared. Channel activation parameters were shifted in a hyperpolarizing direction in the mutant channel, whereas inactivation parameters were shifted in a depolarizing direction, increasing Na channel window current. Macroscopic current decay was slowed in I1327V channels, indicating an impairment in the transition from open state to inactivated state. Channel deactivation was also delayed, allowing more channels to remain in the open state. Phenytoin (100 μm) resulted in hyperpolarized activation and inactivation curves as well as greater tonic block and use-dependent block of I1327V mutant channels relative to WT. SCN8A - I1327V is a gain-of-function mutation with altered features that are predicted to increase neuronal excitability and seizure susceptibility. Phenytoin is an effective inhibitor of the mutant channel and may be of use in treating patients with gain-of-function mutations of SCN8A. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin

PubMed Central

Barker, Bryan S.; Ottolini, Matteo; Wagnon, Jacy L.; Hollander, Rachel; Meisler, Miriam H.; Patel, Manoj K.

2016-01-01

Objective SCN8A encephalopathy (EIEE13) is caused by gain-of-function mutations resulting in hyperactivity of the voltage-gated sodium channel Nav1.6. The channel is concentrated at the axon initial segment (AIS) and is involved in establishing neuronal excitability. Clinical features of SCN8A encephalopathy include seizure onset between 0–18 months of age, intellectual disability, and developmental delay. Seizures are often refractory to treatment with standard anti-epileptic drugs, and sudden unexpected death in epilepsy (SUDEP) has been reported in approximately 10% of patients. In a recent study, high doses of phenytoin were effective in four patients with SCN8A encephalopathy. In view of this observation, we have investigated the relationship between the functional effect of the SCN8A mutation p.Ile1327Val and its response to phenytoin. Methods The mutation was introduced into the Scn8a cDNA by site-directed mutagenesis. Channel activity was characterized in transfected ND7/23 cells. The effects of phenytoin (100 μM) on mutant and wild type (WT) channels were compared. Results Channel activation parameters were shifted in a hyperpolarizing direction in the mutant channel, while inactivation parameters were shifted in a depolarizing direction, increasing Na channel window current. Macroscopic current decay was slowed in I1327V channels, indicating an impairment in the transition from open state to inactivated state. Channel deactivation was also delayed, allowing more channels to remain in the open state. Phenytoin (100 μM) resulted in hyperpolarized activation and inactivation curves as well as greater tonic block and use dependent block of I1327V mutant channels relative to WT. Significance SCN8A – I1327V is a gain-of-function mutation with altered features that are predicted to increase neuronal excitability and seizure susceptibility. Phenytoin is an effective inhibitor of the mutant channel and may be of use in treating patients with gain-of-function mutations of SCN8A. PMID:27375106

A Direct Comparison of Self-Injurious and Stereotyped Motor Behavior Between Preschool-Aged Children With and Without Developmental Delays

PubMed Central

Spofford, Lisa; Dimian, Adele; Tervo, Raymond; MacLean, William E.; Symons, Frank J.

2016-01-01

Objective To compare the prevalence of self-injurious behavior (SIB) and stereotyped motor behavior (STY) of preschool-aged children with developmental delays (DD group) and their peers without developmental delays (TD group) using a standardized caregiver report scale. Methods The Repetitive Behavior Scale-Revised was completed by caregivers of children with developmental delays and their peers without developmental delays. Frequency of occurrence and severity ratings for SIB and STY were compared between groups. Results SIB and STY were reported more often and at a greater level of severity in the DD group. Older chronological age was associated with more severe STY in the DD group but not the TD group. Gender was not related to STY or SIB for either group. Conclusions Differences in STY and SIB were evident between preschoolers with and without DD. Findings are discussed from developmental and behavioral psychology perspectives regarding the expression of repetitive behavior in developmentally at-risk pediatric populations. PMID:26514642

Editorial brain malformation surveillance in the Zika era

PubMed Central

Trevathan, Edwin

2016-01-01

The current surveillance systems for congenital microcephaly are necessary to monitor the impact of Zika virus (ZIKV) on the developing human brain, as well as the ZIKV prevention efforts. However, these congenital microcephaly surveillance systems are insufficient. Abnormalities of neuronal differentiation, development and migration may occur among infants with normal head circumference who have intrauterine exposure to ZIKV. Therefore, surveillance for congenital microcephaly does not ascertain many of the infants seriously impacted by congenital ZIKV infection. Furthermore, many infants with normal head circumference and with malformations of the brain cortex do not have clinical manifestations of their congenital malformations until several months to many years after birth, when they present with clinical manifestations such as seizures/epilepsy, developmental delays with or without developmental regression, and/or motor impairment. In response to the ZIKV threat, public health surveillance systems must be enhanced to ascertain a wide variety of congenital brain malformations, as well as their clinical manifestations that lead to diagnostic brain imaging. Birth Defects Research (Part A) 106:869–874, 2016. © 2016 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc. PMID:27891785

Sleep Problems and Early Developmental Delay: Implications for Early Intervention Programs

ERIC Educational Resources Information Center

Bonuck, Karen; Grant, Roy

2012-01-01

Sleep disorders negatively impact behavior, cognition, and growth--the same areas targeted by early intervention. Conversely, developmental delays and disabilities may themselves precipitate sleep disorders. Young children with developmental delays experience sleep disorders at a higher rate than do typically developing children; the most common…

Delaying Developmental Mathematics: The Characteristics and Costs

ERIC Educational Resources Information Center

Johnson, Marianne; Kuennen, Eric

2004-01-01

This paper investigates which students delay taking a required developmental mathematics course and the impact of delay on student performance in introductory microeconomics. Analysis of a sample of 1462 students at a large Midwestern university revealed that, although developmental-level mathematics students did not reach the same level of…

Mutations in HIVEP2 are associated with developmental delay, intellectual disability, and dysmorphic features.

PubMed

Steinfeld, Hallie; Cho, Megan T; Retterer, Kyle; Person, Rick; Schaefer, G Bradley; Danylchuk, Noelle; Malik, Saleem; Wechsler, Stephanie Burns; Wheeler, Patricia G; van Gassen, Koen L I; Terhal, P A; Verhoeven, Virginie J M; van Slegtenhorst, Marjon A; Monaghan, Kristin G; Henderson, Lindsay B; Chung, Wendy K

2016-07-01

Human immunodeficiency virus type I enhancer binding protein 2 (HIVEP2) has been previously associated with intellectual disability and developmental delay in three patients. Here, we describe six patients with developmental delay, intellectual disability, and dysmorphic features with de novo likely gene-damaging variants in HIVEP2 identified by whole-exome sequencing (WES). HIVEP2 encodes a large transcription factor that regulates various neurodevelopmental pathways. Our findings provide further evidence that pathogenic variants in HIVEP2 lead to intellectual disabilities and developmental delay.

Ictal high frequency oscillations distinguish two types of seizure territories in humans

PubMed Central

Weiss, Shennan A.; Banks, Garrett P.; McKhann, Guy M.; Goodman, Robert R.; Emerson, Ronald G.; Trevelyan, Andrew J.

2013-01-01

High frequency oscillations have been proposed as a clinically useful biomarker of seizure generating sites. We used a unique set of human microelectrode array recordings (four patients, 10 seizures), in which propagating seizure wavefronts could be readily identified, to investigate the basis of ictal high frequency activity at the cortical (subdural) surface. Sustained, repetitive transient increases in high gamma (80–150 Hz) amplitude, phase-locked to the low-frequency (1–25 Hz) ictal rhythm, correlated with strong multi-unit firing bursts synchronized across the core territory of the seizure. These repetitive high frequency oscillations were seen in recordings from subdural electrodes adjacent to the microelectrode array several seconds after seizure onset, following ictal wavefront passage. Conversely, microelectrode recordings demonstrating only low-level, heterogeneous neural firing correlated with a lack of high frequency oscillations in adjacent subdural recording sites, despite the presence of a strong low-frequency signature. Previously, we reported that this pattern indicates a failure of the seizure to invade the area, because of a feedforward inhibitory veto mechanism. Because multi-unit firing rate and high gamma amplitude are closely related, high frequency oscillations can be used as a surrogate marker to distinguish the core seizure territory from the surrounding penumbra. We developed an efficient measure to detect delayed-onset, sustained ictal high frequency oscillations based on cross-frequency coupling between high gamma amplitude and the low-frequency (1–25 Hz) ictal rhythm. When applied to the broader subdural recording, this measure consistently predicted the timing or failure of ictal invasion, and revealed a surprisingly small and slowly spreading seizure core surrounded by a far larger penumbral territory. Our findings thus establish an underlying neural mechanism for delayed-onset, sustained ictal high frequency oscillations, and provide a practical, efficient method for using them to identify the small ictal core regions. Our observations suggest that it may be possible to reduce substantially the extent of cortical resections in epilepsy surgery procedures without compromising seizure control. PMID:24176977

SCN2A encephalopathy

PubMed Central

Howell, Katherine B.; McMahon, Jacinta M.; Carvill, Gemma L.; Tambunan, Dimira; Mackay, Mark T.; Rodriguez-Casero, Victoria; Webster, Richard; Clark, Damian; Freeman, Jeremy L.; Calvert, Sophie; Olson, Heather E.; Mandelstam, Simone; Poduri, Annapurna; Mefford, Heather C.; Harvey, A. Simon

2015-01-01

Objective: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies. Herein, we define the phenotypic spectrum of SCN2A encephalopathy. Methods: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping. Results: Patients were aged 0.7 to 22 years; 3 were deceased. Seizures commenced on day 1–4 in 8, week 2–6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset. Multifocal interictal epileptiform discharges were seen in all. Three of 12 patients had infantile spasms. The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment. Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms. Mutations arose de novo in 11 patients; paternal DNA was unavailable in one. Conclusions: Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile–onset groups with severe and intermediate outcomes, and a childhood-onset group. Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome. Sodium channel blockers, particularly phenytoin, may improve seizure control. PMID:26291284

Haploinsufficiency of CELF4 at 18q12.2 is associated with developmental and behavioral disorders, seizures, eye manifestations, and obesity

PubMed Central

Halgren, Christina; Bache, Iben; Bak, Mads; Myatt, Mikkel Wanting; Anderson, Claire Marie; Brøndum-Nielsen, Karen; Tommerup, Niels

2012-01-01

Only 20 patients with deletions of 18q12.2 have been reported in the literature and the associated phenotype includes borderline intellectual disability, behavioral problems, seizures, obesity, and eye manifestations. Here, we report a male patient with a de novo translocation involving chromosomes 12 and 18, with borderline IQ, developmental and behavioral disorders, myopia, obesity, and febrile seizures in childhood. We characterized the rearrangement with Affymetrix SNP 6.0 Array analysis and next-generation mate pair sequencing and found truncation of CELF4 at 18q12.2. This second report of a patient with a neurodevelopmental phenotype and a translocation involving CELF4 supports that CELF4 is responsible for the phenotype associated with deletion of 18q12.2. Our study illustrates the utility of high-resolution genome-wide techniques in identifying neurodevelopmental and neurobehavioral genes, and it adds to the growing evidence, including a transgenic mouse model, that CELF4 is important for human brain development. PMID:22617346

Bumetanide enhances phenobarbital efficacy in a rat model of hypoxic neonatal seizures.

PubMed

Cleary, Ryan T; Sun, Hongyu; Huynh, Thanhthao; Manning, Simon M; Li, Yijun; Rotenberg, Alexander; Talos, Delia M; Kahle, Kristopher T; Jackson, Michele; Rakhade, Sanjay N; Berry, Gerard T; Berry, Gerard; Jensen, Frances E

2013-01-01

Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na(+)-K(+)-2 Cl(-) cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABAA receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in EGABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures.

Bumetanide Enhances Phenobarbital Efficacy in a Rat Model of Hypoxic Neonatal Seizures

PubMed Central

Cleary, Ryan T.; Sun, Hongyu; Huynh, Thanhthao; Manning, Simon M.; Li, Yijun; Rotenberg, Alexander; Talos, Delia M.; Kahle, Kristopher T.; Jackson, Michele; Rakhade, Sanjay N.; Berry, Gerard; Jensen, Frances E.

2013-01-01

Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na+-K+-2 Cl− cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABAA receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in EGABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures. PMID:23536761

Selective head cooling during neonatal seizures prevents postictal cerebral vascular dysfunction without reducing epileptiform activity

PubMed Central

Harsono, Mimily; Pourcyrous, Massroor; Jolly, Elliott J.; de Jongh Curry, Amy; Fedinec, Alexander L.; Liu, Jianxiong; Basuroy, Shyamali; Zhuang, Daming; Leffler, Charles W.

2016-01-01

Epileptic seizures in neonates cause cerebrovascular injury and impairment of cerebral blood flow (CBF) regulation. In the bicuculline model of seizures in newborn pigs, we tested the hypothesis that selective head cooling prevents deleterious effects of seizures on cerebral vascular functions. Preventive or therapeutic ictal head cooling was achieved by placing two head ice packs during the preictal and/or ictal states, respectively, for the ∼2-h period of seizures. Head cooling lowered the brain and core temperatures to 25.6 ± 0.3 and 33.5 ± 0.1°C, respectively. Head cooling had no anticonvulsant effects, as it did not affect the bicuculline-evoked electroencephalogram parameters, including amplitude, duration, spectral power, and spike frequency distribution. Acute and long-term cerebral vascular effects of seizures in the normothermic and head-cooled groups were tested during the immediate (2–4 h) and delayed (48 h) postictal periods. Seizure-induced cerebral vascular injury during the immediate postictal period was detected as terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive staining of cerebral arterioles and a surge of brain-derived circulating endothelial cells in peripheral blood in the normothermic group, but not in the head-cooled groups. During the delayed postictal period, endothelium-dependent cerebral vasodilator responses were greatly reduced in the normothermic group, indicating impaired CBF regulation. Preventive or therapeutic ictal head cooling mitigated the endothelial injury and greatly reduced loss of postictal cerebral vasodilator functions. Overall, head cooling during seizures is a clinically relevant approach to protecting the neonatal brain by preventing cerebrovascular injury and the loss of the endothelium-dependent control of CBF without reducing epileptiform activity. PMID:27591217

Correlation between EEG abnormalities and symptoms of autism spectrum disorder (ASD).

PubMed

Yasuhara, Akihiro

2010-11-01

Children with ASD often suffer from epilepsy and paroxysmal EEG abnormality. Purposes of this study are the confirmation of incidence of epileptic seizures and EEG abnormalities in children with autism using a high performance digital EEG, to examine the nature of EEG abnormalities such as locus or modality, and to determine if the development of children with ASD, who have experienced developmental delay, improves when their epilepsy has been treated and maintained under control. A total of 1014 autistic children that have been treated and followed-up for more than 3 years at Yasuhara Children's Clinic in Osaka, Japan, were included in this study. Each participant's EEG had been recorded approximately every 6 months under sleep conditions. Epilepsy was diagnosed in 37% (375/1014) of the study participants. Almost all patients diagnosed with epilepsy presented with symptomatic epilepsy. The data showed that the participants with lower IQ had a higher incidence of epileptic seizures. Epileptic EEG discharges occurred in 85.8% (870/1014) of the patients. There was also a very high incidence of spike discharges in participants whose intellectual quotient was very low or low. Epileptic seizure waves most frequently developed from the frontal lobe (65.6%), including the front pole (Fp1 and Fp2), frontal part (F3, F4, F7 and F8) and central part (C3, Cz and C4). The occurrence rate of spike discharges in other locations, including temporal lobe (T3, T4, T5, T6), parietal lobe (P3, Pz, P4), occipital lobe (O1, O2) and multifocal spikes was less than 10%. These results support the notion that there is a relationship between ASD and dysfunction of the mirror neuron system. The management of seizure waves in children diagnosed with ASD may result in improves function and reduction of autistic symptoms. Copyright © 2010 Elsevier B.V. All rights reserved.

The Diagnostic Yield of Array Comparative Genomic Hybridization Is High Regardless of Severity of Intellectual Disability/Developmental Delay in Children.

PubMed

D'Arrigo, Stefano; Gavazzi, Francesco; Alfei, Enrico; Zuffardi, Orsetta; Montomoli, Cristina; Corso, Barbara; Buzzi, Erika; Sciacca, Francesca L; Bulgheroni, Sara; Riva, Daria; Pantaleoni, Chiara

2016-05-01

Microarray-based comparative genomic hybridization is a method of molecular analysis that identifies chromosomal anomalies (or copy number variants) that correlate with clinical phenotypes. The aim of the present study was to apply a clinical score previously designated by de Vries to 329 patients with intellectual disability/developmental disorder (intellectual disability/developmental delay) referred to our tertiary center and to see whether the clinical factors are associated with a positive outcome of aCGH analyses. Another goal was to test the association between a positive microarray-based comparative genomic hybridization result and the severity of intellectual disability/developmental delay. Microarray-based comparative genomic hybridization identified structural chromosomal alterations responsible for the intellectual disability/developmental delay phenotype in 16% of our sample. Our study showed that causative copy number variants are frequently found even in cases of mild intellectual disability (30.77%). We want to emphasize the need to conduct microarray-based comparative genomic hybridization on all individuals with intellectual disability/developmental delay, regardless of the severity, because the degree of intellectual disability/developmental delay does not predict the diagnostic yield of microarray-based comparative genomic hybridization. © The Author(s) 2015.

Neurodevelopmental Outcome and Treatment Efficacy of Benzoate and Dextromethorphan in Siblings with Attenuated Nonketotic Hyperglycinemia.

PubMed

Bjoraker, Kendra J; Swanson, Michael A; Coughlin, Curtis R; Christodoulou, John; Tan, Ee S; Fergeson, Mark; Dyack, Sarah; Ahmad, Ayesha; Friederich, Marisa W; Spector, Elaine B; Creadon-Swindell, Geralyn; Hodge, M Antoinette; Gaughan, Sommer; Burns, Casey; Van Hove, Johan L K

2016-03-01

To evaluate the impact of sodium benzoate and dextromethorphan treatment on patients with the attenuated form of nonketotic hyperglycinemia. Families were recruited with 2 siblings both affected with attenuated nonketotic hyperglycinemia. Genetic mutations were expressed to identify residual activity. The outcome on developmental progress and seizures was compared between the first child diagnosed and treated late with the second child diagnosed at birth and treated aggressively from the newborn period using dextromethorphan and benzoate at dosing sufficient to normalize plasma glycine levels. Both siblings were evaluated with similar standardized neurodevelopmental measures. In each sibling set, the second sibling treated from the neonatal period achieved earlier and more developmental milestones, and had a higher developmental quotient. In 3 of the 4 sibling pairs, the younger sibling had no seizures whereas the first child had a seizure disorder. The adaptive behavior subdomains of socialization and daily living skills improved more than motor skills and communication. Early treatment with dextromethorphan and sodium benzoate sufficient to normalize plasma glycine levels is effective at improving outcome if used in children with attenuated disease with mutations providing residual activity and when started from the neonatal period. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Developmental Coordination Disorder in a Patient with Mental Disability and a Mild Phenotype Carrying Terminal 6q26-qter Deletion

PubMed Central

De Cinque, Marianna; Palumbo, Orazio; Mazzucco, Ermelinda; Simone, Antonella; Palumbo, Pietro; Ciavatta, Renata; Maria, Giuliana; Ferese, Rosangela; Gambardella, Stefano; Angiolillo, Antonella; Carella, Massimo; Garofalo, Silvio

2017-01-01

Terminal deletion of chromosome 6q is a rare chromosomal abnormality associated with variable phenotype spectrum. Although intellectual disability, facial dysmorphism, seizures and brain abnormalities are typical features of this syndrome, genotype–phenotype correlation needs to be better understood. We report the case of a 6-year-old Caucasian boy with a clinical diagnosis of intellectual disability, delayed language development and dyspraxia who carries an approximately 8 Mb de novo heterozygous microdeletion in the 6q26-q27 locus identified by karyotype and defined by high-resolution SNP-array analysis. This patient has no significant structural brain or other organ malformation, and he shows a very mild phenotype compared to similar 6q26-qter deletion. The patient phenotype also suggests that a dyspraxia susceptibility gene is located among the deleted genes. PMID:29270193

Leukoencephalopathy with thalamus and brainstem involvement and high lactate caused by novel mutations in the EARS2 gene in two siblings.

PubMed

Şahin, Sevim; Cansu, Ali; Kalay, Ersan; Dinçer, Tuba; Kul, Sibel; Çakır, İsmet Miraç; Kamaşak, Tülay; Budak, Gülden Yorgancıoğlu

2016-06-15

Leukoencephalopathy with thalamus and brainstem involvement, and high lactate (LTBL) is a recently identified disease related to mutations in the EARS2 gene encoding glutamyl-tRNA synthetase. We report clinical and radiological findings for two siblings with new pathogenic mutations in the EARS2 gene. Both patients showed symptoms of mild-type disease, but there were clinical differences between the two siblings. While the older brother had hypotonia and delayed developmental milestones, the younger brother had seizures and spasticity in the lower extremities. Brain magnetic resonance imaging (MRI) findings were quite similar for the two siblings. MRI findings were specific to LTBL. MRI lesions of the older sibling had regressed over time. Clinical and radiological improvement, as in the previously reported patients with LTBL, may be an important clue for diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

SIFD as a novel cause of severe fetal hydrops and neonatal anaemia with iron loading and marked extramedullary haemopoiesis.

PubMed

Barton, Chris; Kausar, Sabiha; Kerr, Deborah; Bitetti, Stefania; Wynn, Rob

2018-03-01

SIFD describes a heritable, syndromic condition characterised principally by sideroblastic anaemia (SA) with immunodeficiency, fevers and developmental delay, arising in mutations within the TRNT1 gene. Other clinical manifestations of SIFD include cardiomyopathy, seizures, sensorineural hearing loss, renal dysfunction, metabolic abnormalities, hepatosplenomegaly and retinitis pigmentosa.Presentation of SIFD is variable but typically in early childhood with SA or with fever. In this report, we extend the described SIFD phenotype. We describe a kindred in which the index case presented with fetal hydrops, and early neonatal death, and the second child had severe anaemia at delivery. Both cases had prominent extramedullary erythropoiesis and numerous circulating nucleated red blood cells. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Mitochondrial Dysfunction Plus High-Sugar Diet Provokes a Metabolic Crisis That Inhibits Growth.

PubMed

Kemppainen, Esko; George, Jack; Garipler, Görkem; Tuomela, Tea; Kiviranta, Essi; Soga, Tomoyoshi; Dunn, Cory D; Jacobs, Howard T

2016-01-01

The Drosophila mutant tko25t exhibits a deficiency of mitochondrial protein synthesis, leading to a global insufficiency of respiration and oxidative phosphorylation. This entrains an organismal phenotype of developmental delay and sensitivity to seizures induced by mechanical stress. We found that the mutant phenotype is exacerbated in a dose-dependent fashion by high dietary sugar levels. tko25t larvae were found to exhibit severe metabolic abnormalities that were further accentuated by high-sugar diet. These include elevated pyruvate and lactate, decreased ATP and NADPH. Dietary pyruvate or lactate supplementation phenocopied the effects of high sugar. Based on tissue-specific rescue, the crucial tissue in which this metabolic crisis initiates is the gut. It is accompanied by down-regulation of the apparatus of cytosolic protein synthesis and secretion at both the RNA and post-translational levels, including a novel regulation of S6 kinase at the protein level.

Mitochondrial Dysfunction Plus High-Sugar Diet Provokes a Metabolic Crisis That Inhibits Growth

PubMed Central

Kemppainen, Esko; George, Jack; Garipler, Görkem; Tuomela, Tea; Kiviranta, Essi; Soga, Tomoyoshi; Dunn, Cory D.; Jacobs, Howard T.

2016-01-01

The Drosophila mutant tko25t exhibits a deficiency of mitochondrial protein synthesis, leading to a global insufficiency of respiration and oxidative phosphorylation. This entrains an organismal phenotype of developmental delay and sensitivity to seizures induced by mechanical stress. We found that the mutant phenotype is exacerbated in a dose-dependent fashion by high dietary sugar levels. tko25t larvae were found to exhibit severe metabolic abnormalities that were further accentuated by high-sugar diet. These include elevated pyruvate and lactate, decreased ATP and NADPH. Dietary pyruvate or lactate supplementation phenocopied the effects of high sugar. Based on tissue-specific rescue, the crucial tissue in which this metabolic crisis initiates is the gut. It is accompanied by down-regulation of the apparatus of cytosolic protein synthesis and secretion at both the RNA and post-translational levels, including a novel regulation of S6 kinase at the protein level. PMID:26812173

Encephalopathy in an infant with infantile spasms: possible role of valproate toxicity

PubMed Central

Sivathanu, Shobhana; Sampath, Sowmya; Veerasamy, Madhubala; Sunderkumar, Satheeshkumar

2014-01-01

An infant presented with global developmental delay and infantile spasms. EEG was suggestive of hypsarrhythmia. She was started on sodium valproate, clonazepam and adrenocorticotropic hormone injection. After an initial improvement the child developed vomiting, altered sensorium and increase in frequency of seizures suggestive of encephalopathy. Valproate-induced hyperammonaemia or hepatic encephalopathy was considered and the drug was withheld following which there was a dramatic improvement. Paradoxically, the liver function tests and serum ammonia were normal. However, a complete reversal of encephalopathy, on withdrawal of the drug, strongly suggested an adverse drug reaction (ADR) due to valproic acid. Marginal elevation of serum valproic acid prompted us to use the Naranjo ADR probability score to confirm the diagnosis. This case highlights the fact that valproate toxicity can manifest with normal liver function and serum ammonia levels. This is the youngest reported case with this rare form of valproate-induced encephalopathy. PMID:24810446

Magnetic resonance imaging (MRI) evaluation of developmental delay in pediatric patients.

PubMed

Ali, Althaf S; Syed, Naziya P; Murthy, G S N; Nori, Madhavi; Abkari, Anand; Pooja, B K; Venkateswarlu, J

2015-01-01

Developmental delay is defined as significant delay in one or more developmental domains. Magnetic Resonance Imaging (MRI) is the best modality to investigate such patients. Evaluation of a child with developmental delay is important not only because it allows early diagnosis and treatment but also helpful for parental counseling regarding the outcome of their child and to identify any possible risk of recurrence in the siblings. Thus this study was undertaken to evaluate the developmental delay in Indian children which will help the clinicians in providing an estimation of the child's ultimate developmental potential and organize specific treatment requirement and also relieve parental apprehension. To study the prevalence of normal and abnormal MRI in pediatric patients presenting with developmental delay and further categorize the abnormal MRI based on its morphological features. It is a prospective, observational & descriptive study of MRI Brain in 81 paediatric patients (46 Males and 35 Females), aged between three months to 12 years; presenting with developmental delay in Deccan College of Medical Sciences, Hyderabad; over a period of three years (Sept 2011 to Sept 2014). MRI brain was done on 1.5T Siemens Magnetom Essenza & 0.35T Magnetom C with appropriate sequences and planes after making the child sleep/sedated/ anesthetized. Various anatomical structures like Ventricles, Corpus callosum, etc were systematically assessed. The MRI findings were divided into various aetiological subgroups. Normal MRI findings were seen in 32% cases and 68% had abnormal findings of which the proportion of Traumatic/ Neurovascular Diseases, Congenital & Developmental, Metabolic and Degenerative, neoplastic and non specific were 31%, 17%, 10%, 2.5% and 7.5% respectively. The ventricles and white matter mainly the corpus callosum were the most commonly affected anatomical structures. The diagnostic yield was found to be 68% and higher yield was seen in patients presenting with developmental delay plus. The clinical diagnosis of developmental delay should not be the end point, but rather a springboard for an effective search for causal factors. MRI is the best investigation with a high yield in such patients.

Magnetic Resonance Imaging (MRI) Evaluation of Developmental Delay in Pediatric Patients

PubMed Central

Syed, Naziya P.; Murthy, G.S.N.; Nori, Madhavi; Abkari, Anand; Pooja, B.K.; Venkateswarlu, J.

2015-01-01

Introduction: Developmental delay is defined as significant delay in one or more developmental domains. Magnetic Resonance Imaging (MRI) is the best modality to investigate such patients. Evaluation of a child with developmental delay is important not only because it allows early diagnosis and treatment but also helpful for parental counseling regarding the outcome of their child and to identify any possible risk of recurrence in the siblings. Thus this study was undertaken to evaluate the developmental delay in Indian children which will help the clinicians in providing an estimation of the child’s ultimate developmental potential and organize specific treatment requirement and also relieve parental apprehension. Aims and Objectives: To study the prevalence of normal and abnormal MRI in pediatric patients presenting with developmental delay and further categorize the abnormal MRI based on its morphological features. Materials and Methods: It is a prospective, observational & descriptive study of MRI Brain in 81 paediatric patients (46 Males and 35 Females), aged between three months to 12 years; presenting with developmental delay in Deccan College of Medical Sciences, Hyderabad; over a period of three years (Sept 2011 to Sept 2014). MRI brain was done on 1.5T Siemens Magnetom Essenza & 0.35T Magnetom C with appropriate sequences and planes after making the child sleep/sedated/ anesthetized. Various anatomical structures like Ventricles, Corpus callosum, etc were systematically assessed. The MRI findings were divided into various aetiological subgroups. Results: Normal MRI findings were seen in 32% cases and 68% had abnormal findings of which the proportion of Traumatic/ Neurovascular Diseases, Congenital & Developmental, Metabolic and Degenerative, neoplastic and non specific were 31%, 17%, 10%, 2.5% and 7.5% respectively. The ventricles and white matter mainly the corpus callosum were the most commonly affected anatomical structures. The diagnostic yield was found to be 68% and higher yield was seen in patients presenting with developmental delay plus. Conclusion: The clinical diagnosis of developmental delay should not be the end point, but rather a springboard for an effective search for causal factors. MRI is the best investigation with a high yield in such patients. PMID:25738057

Could head circumference be used to screen for autism in young males with developmental delay?

PubMed

Gray, Kylie M; Taffe, John; Sweeney, Deborah J; Forster, Sheridan; Tonge, Bruce J

2012-04-01

Research has suggested an abnormal acceleration in head circumference growth in children with autism within the first 12 months of life. This study aimed to examine head circumference at birth and head circumference growth rates in young children with autism and developmental delay, and young children with developmental delay without autism. This study assessed head circumference at birth and rate of change in head circumference in young children with autism (n=86) and children with developmental delay without autism (n=40). For both groups of children, head circumference at birth and head circumference growth were compared with Centers for Disease Control normative data. No differences were found between the group of children with autism and developmental delay compared with the group with developmental delay only. However, when the sample was compared with a range of selected Centers for Disease Control normative medians, the children with autism were found to have significantly smaller head circumferences at birth and significantly larger head circumference at 18.5 months of age. These results are discussed in relation to the potential of accelerated head circumference growth as an early marker for autism. This study failed to find a difference in the head circumferences of children with autism and developmental delay and children with developmental delay only, thus suggesting that head circumference measurement has limited value as an early marker for autism. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Epoxy Fatty Acids and Inhibition of the Soluble Epoxide Hydrolase Selectively Modulate GABA Mediated Neurotransmission to Delay Onset of Seizures

PubMed Central

Inceoglu, Bora; Zolkowska, Dorota; Yoo, Hyun Ju; Wagner, Karen M.; Yang, Jun; Hackett, Edward; Hwang, Sung Hee; Lee, Kin Sing Stephen; Rogawski, Michael A.; Morisseau, Christophe; Hammock, Bruce D.

2013-01-01

In the brain, seizures lead to release of large amounts of polyunsaturated fatty acids including arachidonic acid (ARA). ARA is a substrate for three major enzymatic routes of metabolism by cyclooxygenase, lipoxygenase and cytochrome P450 enzymes. These enzymes convert ARA to potent lipid mediators including prostanoids, leukotrienes and epoxyeicosatrienoic acids (EETs). The prostanoids and leukotrienes are largely pro-inflammatory molecules that sensitize neurons whereas EETs are anti-inflammatory and reduce the excitability of neurons. Recent evidence suggests a GABA-related mode of action potentially mediated by neurosteroids. Here we tested this hypothesis using models of chemically induced seizures. The level of EETs in the brain was modulated by inhibiting the soluble epoxide hydrolase (sEH), the major enzyme that metabolizes EETs to inactive molecules, by genetic deletion of sEH and by direct administration of EETs into the brain. All three approaches delayed onset of seizures instigated by GABA antagonists but not seizures through other mechanisms. Inhibition of neurosteroid synthesis by finasteride partially blocked the anticonvulsant effects of sEH inhibitors while the efficacy of an inactive dose of neurosteroid allopregnanolone was enhanced by sEH inhibition. Consistent with earlier findings, levels of prostanoids in the brain were elevated. In contrast, levels of bioactive EpFAs were decreased following seizures. Overall these results demonstrate that EETs are natural molecules which suppress the tonic component of seizure related excitability through modulating the GABA activity and that exploration of the EET mediated signaling in the brain could yield alternative approaches to treat convulsive disorders. PMID:24349022

De novo truncating variants in the AHDC1 gene encoding the AT-hook DNA-binding motif-containing protein 1 are associated with intellectual disability and developmental delay.

PubMed

Yang, Hui; Douglas, Ganka; Monaghan, Kristin G; Retterer, Kyle; Cho, Megan T; Escobar, Luis F; Tucker, Megan E; Stoler, Joan; Rodan, Lance H; Stein, Diane; Marks, Warren; Enns, Gregory M; Platt, Julia; Cox, Rachel; Wheeler, Patricia G; Crain, Carrie; Calhoun, Amy; Tryon, Rebecca; Richard, Gabriele; Vitazka, Patrik; Chung, Wendy K

2015-10-01

Whole-exome sequencing (WES) represents a significant breakthrough in clinical genetics, and identifies a genetic etiology in up to 30% of cases of intellectual disability (ID). Using WES, we identified seven unrelated patients with a similar clinical phenotype of severe intellectual disability or neurodevelopmental delay who were all heterozygous for de novo truncating variants in the AT-hook DNA-binding motif-containing protein 1 (AHDC1). The patients were all minimally verbal or nonverbal and had variable neurological problems including spastic quadriplegia, ataxia, nystagmus, seizures, autism, and self-injurious behaviors. Additional common clinical features include dysmorphic facial features and feeding difficulties associated with failure to thrive and short stature. The AHDC1 gene has only one coding exon, and the protein contains conserved regions including AT-hook motifs and a PDZ binding domain. We postulate that all seven variants detected in these patients result in a truncated protein missing critical functional domains, disrupting interactions with other proteins important for brain development. Our study demonstrates that truncating variants in AHDC1 are associated with ID and are primarily associated with a neurodevelopmental phenotype.

Visualizing the Comorbidity Burden in Children with Autism Spectrum Disorder Receiving Dental Treatment Under General Anesthesia.

PubMed

Mathu-Muju, Kavita R; Li, Hsin-Fang; Nam, Lisa H; Bush, Heather M

2016-01-01

The purposes of this study were to: (1) describe the comorbidity burden in children with autism spectrum disorder (ASD) receiving dental treatment under general anesthesia (GA); and (2) characterize the complexity of these concurrent comorbidities. A retrospective chart review was completed of 303 children with ASD who received dental treatment under GA. All comorbidities, in addition to the primary diagnosis of ASD, were categorized using the International Classification of Diseases-10 codes. The interconnectedness of the comorbidities was graphically displayed using a network plot. Network indices (degree centrality, betweenness centrality, closeness centrality) were used to characterize the comorbidities that exhibited the highest connectedness to ASD. The network plot of medical diagnoses for children with ASD was highly complex, with multiple connected comorbidities. Developmental delay, speech delay, intellectual disability, and seizure disorders exhibited the highest connectedness to ASD. Children with autism spectrum disorder may have a significant comorbidity burden of closely related neurodevelopmental disorders. The medical history review should assess the severity of these concurrent disorders to evaluate a patient's potential ability to cooperate for dental treatment and to determine appropriate behavior guidance techniques to facilitate the delivery of dental care.

Mutations in SLC1A4, encoding the brain serine transporter, are associated with developmental delay, microcephaly and hypomyelination.

PubMed

Damseh, Nadirah; Simonin, Alexandre; Jalas, Chaim; Picoraro, Joseph A; Shaag, Avraham; Cho, Megan T; Yaacov, Barak; Neidich, Julie; Al-Ashhab, Motee; Juusola, Jane; Bale, Sherri; Telegrafi, Aida; Retterer, Kyle; Pappas, John G; Moran, Ellen; Cappell, Joshua; Anyane Yeboa, Kwame; Abu-Libdeh, Bassam; Hediger, Matthias A; Chung, Wendy K; Elpeleg, Orly; Edvardson, Simon

2015-08-01

L-serine plays an essential role in neuronal development and function. Although a non-essential amino acid, L-serine must be synthesised within the brain because of its poor permeability by the blood-brain barrier. Within the brain, its synthesis is confined to astrocytes, and its shuttle to neuronal cells is performed by a dedicated neutral amino acid transporter, ASCT1. Using exome analysis we identified the recessive mutations, p.E256K, p.L315fs, and p.R457W, in SLC1A4, the gene encoding ASCT1, in patients with developmental delay, microcephaly and hypomyelination; seizure disorder was variably present. When expressed in a heterologous system, the mutations did not affect the protein level at the plasma membrane but abolished or markedly reduced L-serine transport for p.R457W and p.E256K mutations, respectively. Interestingly, p.E256K mutation displayed a lower L-serine and alanine affinity but the same substrate selectivity as wild-type ASCT1. The clinical phenotype of ASCT1 deficiency is reminiscent of defects in L-serine biosynthesis. The data underscore that ASCT1 is essential in brain serine transport. The SLC1A4 p.E256K mutation has a carrier frequency of 0.7% in the Ashkenazi-Jewish population and should be added to the carrier screening panel in this community. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clinical and cytogenetic features of a Potocki-Lupski syndrome with the shortest 0.25Mb microduplication in 17p11.2 including RAI1.

PubMed

Lee, Cha Gon; Park, Sang-Jin; Yim, Shin-Young; Sohn, Young Bae

2013-08-01

Potocki-Lupski syndrome (PTLS [MIM 610883]) is a recently recognized microduplication syndrome associated with 17p11.2. It is characterized by mild facial dysmorphic features, hypermetropia, infantile hypotonia, failure to thrive, mental retardation, autistic spectrum disorders, behavioral abnormalities, sleep apnea, and cardiovascular anomalies. In several studies, the critical PTLS region was deduced to be 1.3Mb in length, and included RAI1 and 17 other genes. We report a 3-year-old Korean boy with the smallest duplication in 17p11.2 and a milder phenotype. He had no family history of neurologic disease or developmental delay and no history of seizure, autistic features, or behavior problems. He showed subtle facial dysmorphic features (dolichocephaly and a mildly asymmetric smile) and flat feet. All laboratory tests were normal and he had no evidence of internal organ anomalies. He was found to have mild intellectual disabilities (full scale IQ 65 on K-WPPSI) and language developmental delay (age of 2.2year-old on PRESS). Array comparative genomic hybridization (CGH) showed about a 0.25Mb microduplication on chromosome 17p11.2 containing four Refseq (NCBI reference sequence) genes, including RAI1 [arr 17p11.2(17,575,978-17,824,623)×3]. When compared with previously reported cases, the milder phenotype of our patient may be associated with the smallest duplication in 17p11.2, 0.25Mb in length. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Updates in the genetic evaluation of the child with global developmental delay or intellectual disability.

PubMed

Flore, Leigh Anne; Milunsky, Jeff M

2012-12-01

Global developmental delay (GDD) and intellectual disability (ID) occur in up to 3% of the general population and are even more commonly encountered in the setting of the pediatric neurology clinic. New advances in technology and in the understanding of genetic disorders have led to changes in the diagnostic approach to a child with unexplained GDD or ID. Chromosomal microarray has become a first-line test for evaluation of patients in this population and has both significantly increased diagnostic yield and introduced new challenges in the interpretation of copy number variants of uncertain significance. The G-banded karyotype is now frequently utilized as an adjunct to the microarray rather than as a first-line test in individuals with GDD or ID. Fragile X DNA testing continues to be recommended in the initial evaluation of the child with GDD or ID. The presence or absence of certain cardinal features (such as microcephaly or macrocephaly, seizures, autism, abnormal neurologic examination, and facial dysmorphism) can be utilized to direct single-gene molecular testing. The availability of next-generation and massively parallel sequencing technologies has enabled the use of genetic testing panels, in which dozens of genes associated with GDD or ID may be rapidly analyzed. Most recently, the clinical availability of whole-genome and whole-exome sequencing has opened new possibilities for the evaluation of individuals with GDD or ID who have previously eluded a genetic diagnosis. Consultation with a medical geneticist is recommended when progressing beyond first-tier analyses to most efficiently prioritize testing. Copyright © 2012 Elsevier Inc. All rights reserved.

Vitamin D Levels in Children and Adolescents with Antiepileptic Drug Treatment

PubMed Central

Baek, Jung-Hyun; Seo, Young-Ho; Kim, Gun-Ha; Kim, Mi-Kyung

2014-01-01

Purpose This study was to evaluate the relationship of 25(OH)D3 levels with anticonvulsant use and other possible factors in epileptic children and adolescents. Materials and Methods We studied 143 patients with epilepsy (90 boys, 53 girls; 11.21±4.49 years), who had been treated with anticonvulsants for more than 1 year. Patients who had taken multiple vitamins before the blood test and those who have the limitation of physical activity (wheelchair-bound) were excluded from the study. We evaluated the difference in vitamin D status according to the type and number of anticonvulsants taken and other factors such as gender, age, intelligence and seizure variables. Results For patients with mental retardation or developmental delay, 25(OH)D3 levels were lower than the levels in patients with normal intelligence quotient levels (p=0.03). 25(OH)D3 levels were lower in patients who had taken anticonvulsants for more than 2 years as compared to those who had taken them for less than 2 years (p=0.03). Those taking oxcarbazepine had significantly lower vitamin D levels than patients taking valproic acid (p=0.01). However, no effects of number of anticonvulsants taken were detectable. More than two-thirds of the patients were diagnosed with osteopenia or osteoporosis in patients showing either vitamin D insufficiency or deficiency. Conclusion The possibility of vitamin D deficiency can be considered in pediatric patients taking anticonvulsants if they have mental retardation or developmental delay or if they have been taking anticonvulsants for more than 2 years or taking hepatic enzyme inducing drugs. PMID:24532512

Case study: child with global developmental delay.

PubMed

Okumakpeyi, Pearline; Lunney, Margaret

2010-01-01

This case study focused on the care of a child with global developmental delay. Data were obtained through the author's clinical practice in long-term care pediatric rehabilitation and literature sources. NANDA-International Classifications, the Nursing Interventions Classification (NIC), and Nursing Outcomes Classification (NOC) were used to identify the appropriate nursing diagnosis, nursing interventions, and patient outcomes. This case study provides the pertinent nursing diagnoses, interventions, and outcomes for a child with global developmental delay. The interdisciplinary team approach and family involvement is addressed. Use of NANDA, NIC, and NOC outcomes constructs for enhancing the care of a child with global developmental delay.

Possible induction of West syndrome by oxcarbazepine therapy in a patient with complex partial seizures.

PubMed

Veerapandiyan, Aravindhan; Singh, Piyush; Mikati, Mohamad A

2012-03-01

Oxcarbazepine has been reported to precipitate myoclonic, generalised tonic-clonic, absence, and complex partial seizures, and carbamazepine to precipitate absences, myoclonic seizures and spasms. Here, we report a one-year, six-month-old girl with complex partial seizures who developed infantile spasms, developmental regression, and hypsarrhythmia during the two weeks directly following initiation of oxcarbazepine (14 mg/kg/day). All of these resolved within a few days after discontinuation of this medication. Although we cannot rule out that the above association may have been coincidental, or that the improvement may have been due to concurrent therapy, this case raises the possibility that oxcarbazepine, like carbamazepine, may precipitate infantile spasms and West syndrome.

Phenobarbital and midazolam increase neonatal seizure-associated neuronal injury.

PubMed

Torolira, Daniel; Suchomelova, Lucie; Wasterlain, Claude G; Niquet, Jerome

2017-07-01

Status epilepticus is common in neonates and infants, and is associated with neuronal injury and adverse developmental outcomes. γ-Aminobutyric acidergic (GABAergic) drugs, the standard treatment for neonatal seizures, can have excitatory effects in the neonatal brain, which may worsen the seizures and their effects. Using a recently developed model of status epilepticus in postnatal day 7 rat pups that results in widespread neuronal injury, we found that the GABA A agonists phenobarbital and midazolam significantly increased status epilepticus-associated neuronal injury in various brain regions. Our results suggest that more research is needed into the possible deleterious effects of GABAergic drugs on neonatal seizures and on excitotoxic neuronal injury in the immature brain. Ann Neurol 2017;82:115-120. © 2017 American Neurological Association.

Pyridoxine-Dependent Epilepsy: An Expanding Clinical Spectrum.

PubMed

van Karnebeek, Clara D M; Tiebout, Sylvia A; Niermeijer, Jikkemien; Poll-The, Bwee Tien; Ghani, Aisha; Coughlin, Curtis R; Van Hove, Johan L K; Richter, Jost Wigand; Christen, Hans Juergen; Gallagher, Renata; Hartmann, Hans; Stockler-Ipsiroglu, Sylvia

2016-06-01

Pyridoxine-dependent epilepsy is a rare autosomal recessive epileptic encephalopathy caused by antiquitin (ALDH7A1) deficiency. In spite of adequate seizure control, 75% of patients suffer intellectual developmental disability. Antiquitin deficiency affects lysine catabolism resulting in accumulation of α-aminoadipic semialdehyde/pyrroline 6' carboxylate and pipecolic acid. Beside neonatal refractory epileptic encephalopathy, numerous neurological manifestations and metabolic/biochemical findings have been reported. We present a phenotypic spectrum of antiquitin deficiency based on a literature review (2006 to 2015) of reports (n = 49) describing the clinical presentation of confirmed patients (n > 200) and a further six patient vignettes. Possible presentations include perinatal asphyxia; neonatal withdrawal syndrome; sepsis; enterocolitis; hypoglycemia; neuroimaging abnormalities (corpus callosum and cerebellar abnormalities, hemorrhage, white matter lesions); biochemical abnormalities (lactic acidosis, electrolyte disturbances, neurotransmitter abnormalities); and seizure response to pyridoxine, pyridoxal-phosphate, and folinic acid dietary interventions. The phenotypic spectrum of pyridoxine-dependent epilepsy is wide, including a myriad of neurological and systemic symptoms. Its hallmark feature is refractory seizures during the first year of life. Given its amenability to treatment with lysine-lowering strategies in addition to pyridoxine supplementation for optimal seizure control and developmental outcomes, early diagnosis of pyridoxine-dependent epilepsy is essential. All infants presenting with unexplained seizures should be screened for antiquitin deficiency by determination of α-aminoadipic semialdehyde/pyrroline 6' carboxylate (in urine, plasma or cerebrospinal fluid) and ALDH7A1 molecular analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

The social context of parenting 3-year-old children with developmental delay in the UK.

PubMed

Emerson, E; Graham, H; McCulloch, A; Blacher, J; Hatton, C; Llewellyn, G

2009-01-01

Children with intellectual or developmental disability have significantly poorer health and mental health than their non-disabled peers and are at high risk of social exclusion. The aim of the present paper is to provide information on the circumstances in which 3-year-old children at risk of intellectual or developmental disability are growing up in the UK. Secondary analysis of data on 12 689 families in English-speaking monolingual households from the first two waves of the UK's Millennium Cohort Study. A total of 440 children (3% of the weighted sample) were identified as being developmentally delayed. When compared with other children, children with developmental delays were more disadvantaged on every indicator of social and economic disadvantage examined. Two out of three children with developmental delays had been exposed to repeated disadvantage as measured by income poverty, material hardship, social housing and receipt of means-tested benefits. The effect of repeated disadvantage on the risk of developmental delay remained after account was taken of parental education and occupational status. Young children with delayed development in the UK are likely to be exposed to repeated socio-economic disadvantage. Implications for policy and understanding the nature of the link between poverty and child disability are discussed.

The child with developmental delay: An approach to etiology

PubMed Central

Meschino, Wendy S

2003-01-01

OBJECTIVE: To describe an approach to history, physical examination and investigation for the developmentally delayed child. METHODS: A review of electronic databases from 1997 to 2001 was done searching for articles relating to the approach to or investigations of children with developmental delay. Five studies, including a review of a consensus conference on evaluation of mental retardation, were chosen because of their general approaches to developmental delay and/or mental retardation, or specific evaluations of a particular laboratory investigation. CONCLUSIONS: A diagnosis or cause of mental retardation can be identified in 20% to 60% of cases. Evaluation of the developmentally delayed child should include a detailed history and physical examination, taking special care to record a three-generation pedigree, as well as to look for dysmorphic features. If no other cause is apparent, routine investigations should include a chromosome study and fragile X studies. Further investigations are warranted depending on the clinical features. PMID:20011550

Coping with Dravet syndrome: parental experiences with a catastrophic epilepsy.

PubMed

Nolan, Kathleen J; Camfield, Carol S; Camfield, Peter R

2006-09-01

The aim of this study was to investigate how parents cope with and care for a child with Dravet syndrome, a severe myoclonic epilepsy with three distinct stages. Twenty-four parents of children with Dravet syndrome participated in a semi-structured interview and 17 completed the Impact of Childhood Neurologic Disability Scale (ICND) questionnaire. Children included 11 males and 13 females aged 2 to 24 years (mean age 10y 2mo [SD 5y 8mo]). Stage 1 of the syndrome was generally very difficult. Uncertainty about the diagnosis was the primary cause of stress. Seizure control was worst during this time. The primary concern in Stage 2 remained seizure control but developmental, behavioral, and sleep issues also emerged. Negative effects were noted in parents' relationships with others. Stage 3 brought better seizure control but decreased cognitive level, increased behavioral problems, and increasing social isolation for parents. Respite and relief care were hard to obtain at each stage. ICND scores mirrored the findings of the interviews. The three stages of Dravet syndrome present serious challenges for parents. Seizures are persistent and severe but developmental, behavioral, and sleep issues add to the stress. In the absence of successful medical treatment for Dravet syndrome, further attention needs to be paid to helping families cope with the disorder.

Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females.

PubMed

Depienne, Christel; Bouteiller, Delphine; Keren, Boris; Cheuret, Emmanuel; Poirier, Karine; Trouillard, Oriane; Benyahia, Baya; Quelin, Chloé; Carpentier, Wassila; Julia, Sophie; Afenjar, Alexandra; Gautier, Agnès; Rivier, François; Meyer, Sophie; Berquin, Patrick; Hélias, Marie; Py, Isabelle; Rivera, Serge; Bahi-Buisson, Nadia; Gourfinkel-An, Isabelle; Cazeneuve, Cécile; Ruberg, Merle; Brice, Alexis; Nabbout, Rima; Leguern, Eric

2009-02-01

Dravet syndrome (DS) is a genetically determined epileptic encephalopathy mainly caused by de novo mutations in the SCN1A gene. Since 2003, we have performed molecular analyses in a large series of patients with DS, 27% of whom were negative for mutations or rearrangements in SCN1A. In order to identify new genes responsible for the disorder in the SCN1A-negative patients, 41 probands were screened for micro-rearrangements with Illumina high-density SNP microarrays. A hemizygous deletion on chromosome Xq22.1, encompassing the PCDH19 gene, was found in one male patient. To confirm that PCDH19 is responsible for a Dravet-like syndrome, we sequenced its coding region in 73 additional SCN1A-negative patients. Nine different point mutations (four missense and five truncating mutations) were identified in 11 unrelated female patients. In addition, we demonstrated that the fibroblasts of our male patient were mosaic for the PCDH19 deletion. Patients with PCDH19 and SCN1A mutations had very similar clinical features including the association of early febrile and afebrile seizures, seizures occurring in clusters, developmental and language delays, behavioural disturbances, and cognitive regression. There were, however, slight but constant differences in the evolution of the patients, including fewer polymorphic seizures (in particular rare myoclonic jerks and atypical absences) in those with PCDH19 mutations. These results suggest that PCDH19 plays a major role in epileptic encephalopathies, with a clinical spectrum overlapping that of DS. This disorder mainly affects females. The identification of an affected mosaic male strongly supports the hypothesis that cellular interference is the pathogenic mechanism.

GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and hyperkinetic and stereotyped movement disorders.

PubMed

Ohba, Chihiro; Shiina, Masaaki; Tohyama, Jun; Haginoya, Kazuhiro; Lerman-Sagie, Tally; Okamoto, Nobuhiko; Blumkin, Lubov; Lev, Dorit; Mukaida, Souichi; Nozaki, Fumihito; Uematsu, Mitsugu; Onuma, Akira; Kodera, Hirofumi; Nakashima, Mitsuko; Tsurusaki, Yoshinori; Miyake, Noriko; Tanaka, Fumiaki; Kato, Mitsuhiro; Ogata, Kazuhiro; Saitsu, Hirotomo; Matsumoto, Naomichi

2015-06-01

Recently, de novo mutations in GRIN1 have been identified in patients with nonsyndromic intellectual disability and epileptic encephalopathy. Whole exome sequencing (WES) analysis of patients with genetically unsolved epileptic encephalopathies identified four patients with GRIN1 mutations, allowing us to investigate the phenotypic spectrum of GRIN1 mutations. Eighty-eight patients with unclassified early onset epileptic encephalopathies (EOEEs) with an age of onset <1 year were analyzed by WES. The effect of mutations on N-methyl-D-aspartate (NMDA) receptors was examined by mapping altered amino acids onto three-dimensional models. We identified four de novo missense GRIN1 mutations in 4 of 88 patients with unclassified EOEEs. In these four patients, initial symptoms appeared within 3 months of birth, including hyperkinetic movements in two patients (2/4, 50%), and seizures in two patients (2/4, 50%). Involuntary movements, severe developmental delay, and intellectual disability were recognized in all four patients. In addition, abnormal eye movements resembling oculogyric crises and stereotypic hand movements were observed in two and three patients, respectively. All the four patients exhibited only nonspecific focal and diffuse epileptiform abnormality, and never showed suppression-burst or hypsarrhythmia during infancy. A de novo mosaic mutation (c.1923G>A) with a mutant allele frequency of 16% (in DNA of blood leukocytes) was detected in one patient. Three mutations were located in the transmembrane domain (3/4, 75%), and one in the extracellular loop near transmembrane helix 1. All the mutations were predicted to impair the function of the NMDA receptor. Clinical features of de novo GRIN1 mutations include infantile involuntary movements, seizures, and hand stereotypies, suggesting that GRIN1 mutations cause encephalopathy resulting in seizures and movement disorders. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Paroxysmal non-epileptic events in infants and toddlers: A phenomenologic analysis.

PubMed

Chen, Li; Knight, Elia M Pestana; Tuxhorn, Ingrid; Shahid, Asim; Lüders, Hans O

2015-06-01

The aim of this study was to analyze in detail the clinical phenomenology of paroxysmal non-epileptic events (PNEE) in infants and toddlers. We studied all children aged ≤2 years who were diagnosed with PNEE based on video-electroencephalographic (VEEG) recordings. We analyzed the following four clinical domains of each clinical event: (i) motor manifestations (body/limb jerking, complex motor, and asymmetric limb posturing); (ii) oral/vocal (crying, vocalization, sighing); (iii) behavioral change (arrest of activity, staring); (iv) and autonomic (facial flushing, breath holding). Thirty-one of 81 (38.3%) infants and toddlers had 38 PNEE recorded during the study period (12 girls and 19 boys, mean age 10.5 months). The predominant clinical features were as follows: motor in 26/38 events, oral/verbal in 14/38 events, behavioral in 11/38 events, and autonomic in 8/38 events. Epileptic seizures and PNEE coexisted in four children (12.9%). Seventeen children (54.8%) had one or more risk factors suggestive of epilepsy. Twelve children (38.7%) had a normal neurologic examination, 10 (32.3%) had developmental delay, and eight (25.8%) had a family history of epilepsy or seizures. VEEG recorded PNEE in nearly 40% of 81 infants and toddlers referred for unclear paroxysmal events in our cohort. Non-epileptic staring spells and benign sleep myoclonus were the most common events recorded, followed by shuddering attacks and infantile masturbation. In addition, greater than one-half of the infants and toddlers had risk factors, raising a concern for epilepsy in the family and prompting the VEEG evaluation, suggesting that paroxysmal non-epileptic seizures may frequently coexist in young children with epilepsy. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Clinical and radiologic features of unilateral and bilateral schizencephaly in polish pediatric patients.

PubMed

Kopyta, Ilona; Jamroz, Ewa; Kluczewska, Ewa; Sarecka-Hujar, Beata

2014-04-01

Schizencephaly is a rare and severe congenital brain defect. Its etiology is not unequivocal and its clinical course differs with every case. The aim of the study was to analyze correlations between clinical and radiologic features of schizencephaly in Polish patients. The study group consisted of 25 children. Epileptic seizures were observed in 60% of cases and in 32% epilepsy was drug resistant. Generalized hypotonia was found in 24%, spastic diparesis in 48%, and spastic hemiparesis in 28% of cases. Seizures were more frequent in the bilateral than unilateral schizencephaly subgroup (72% vs 29%, P = .045). There was a correlation between the presence of the bilateral type II schizencephaly and the occurrence of seizures (P = .002, r = 0.578). There is a correlation between the type of schizencephaly and the presence of seizures in Polish pediatric patients. In most of the patients, schizencephaly leads to developmental retardation and epileptic seizures.

Efficacy of a ketogenic diet in resistant myoclono-astatic epilepsy: A French multicenter retrospective study.

PubMed

Stenger, Elodie; Schaeffer, Mickael; Cances, Claude; Motte, Jacques; Auvin, Stéphane; Ville, Dorothée; Maurey, Hélène; Nabbout, Rima; de Saint-Martin, Anne

2017-03-01

Recent studies have suggested that the early introduction of a ketogenic diet (KD) could improve seizure control in myoclono-astatic epilepsy (MAE). This multicenter study sought to identify the benefits of KD use on seizure control and epilepsy and on developmental outcomes in children with resistant MAE. Fifty children who were diagnosed with severe MAE in the French network of Reference Centers for Rare Epilepsies and who were treated with KD between 2000 and 2013 were included in this study. The seizure frequency and EEG recordings were assessed two weeks before KD introduction, 2 and 6 months after, and during the last follow-up, which also included an assessment of developmental outcome. Patients had a median follow up of 52 months (range 13-136) and received 4.3 antiepileptic drugs [2-9] before KD introduction. Fifty-four percent (54%) of our patients were seizure-free after 6 months of KD or more, and 86% experienced more than a 70% seizure reduction after 2 months of KD. Forty-four percent (44%) of them had a clear benefit of early KD treatment (after four AEDs failed). Early KD treatment did not result in a greater seizure reduction (p=0.055), but significantly resulted in remission (p<0.028). Fifty percent of patients with resistant MAE had normal development outcomes. Earlier KD treatment, after three AEDs failed, was correlated with a better cognitive outcome (p<0.01). Early introduction of KD treatment in resistant MAE has a strong, persistent anticonvulsant effect with long-term remission and better cognitive outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Barriers to Success in Parent Training for Young Children with Developmental Delay: The Role of Cumulative Risk

ERIC Educational Resources Information Center

Bagner, Daniel M.; Graziano, Paulo A.

2013-01-01

The purpose of this study was to examine the effect of cumulative risk on dropout and treatment outcome in parent training. Participants were 44 families of young children (mean age of 49.59 months) who presented with elevated externalizing behavior problems and developmental delay or borderline developmental delay. All families were offered to…

Gender and Geographic Differences in Developmental Delays among Young Children: Analysis of the Data from the National Registry in Taiwan

ERIC Educational Resources Information Center

Lai, Der-Chung; Tseng, Yen-Cheng; Guo, How-Ran

2011-01-01

Although developmental delays are not uncommon in children, the incidence is seldom assessed, and the reported prevalence varies widely. In Taiwan, the government mandates the reporting of suspected cases. Using the national registry data, we conducted a study to estimate the incidence and prevalence of developmental delays in young children in…

Child Care Providers' Competence and Confidence in Referring Children at Risk for Developmental Delays

ERIC Educational Resources Information Center

Branson, Diane; Bingham, Ann

2017-01-01

Despite the benefits of early intervention for children, the majority of children with developmental delays are not identified prior to the age of 5 years. Child care providers could aid in recognition of children at risk for developmental delays; however, there is little research on this topic. This article reports on a qualitative research study…

Parent Pathways: Recognition and Responses to Developmental Delays in Young Children: A Mixed-Methods Exploratory Study

ERIC Educational Resources Information Center

Marshall, Jennifer Tess

2013-01-01

The importance of early recognition and intervention for developmental delays is increasingly acknowledged, yet high rates of under-enrollment and 1-3 year delays in entry to the public early intervention system continue. Much research has examined developmental screening in health and child care settings, but less well understood is what prompts…

Atypical multifocal Dravet syndrome lacks generalized seizures and may show later cognitive decline.

PubMed

Kim, Young Ok; Bellows, Susannah; McMahon, Jacinta M; Iona, Xenia; Damiano, John; Dibbens, Leanne; Kelley, Kent; Gill, Deepak; Cross, J Helen; Berkovic, Samuel F; Scheffer, Ingrid E

2014-01-01

To show that atypical multifocal Dravet syndrome is a recognizable, electroclinical syndrome associated with sodium channel gene (SCN1A) mutations that readily escapes diagnosis owing to later cognitive decline and tonic seizures. Eight patients underwent electroclinical characterization. SCN1A was sequenced and copy number variations sought by multiplex ligation-dependent probe amplification. All patients were female (age range at assessment 5-26y) with median seizure onset at 6.5 months (range 4-19mo). The initial seizure was brief in seven and status epilepticus only occurred in one; three were febrile. Focal seizures occurred in four patients and bilateral convulsion in the other four. All patients developed multiple focal seizure types and bilateral convulsions, with seizure clusters in six. The most common focal seizure semiology (six out of eight) comprised unilateral clonic activity. Five also had focal or asymmetric tonic seizures. Rare or transient myoclonic seizures occurred in six individuals, often triggered by specific antiepileptic drugs. Developmental slowing occurred in all: six between 3 years and 8 years, and two around 1 year 6 months. Cognitive outcome varied from severe to mild intellectual disability. Multifocal epileptiform discharges were seen on electroencephalography. Seven out of eight patients had SCN1A mutations. Atypical, multifocal Dravet syndrome with SCN1A mutations may not be recognized because of later cognitive decline and frequent tonic seizures. © 2013 Mac Keith Press.

Neuregulin-1 is neuroprotective in a rat model of organophosphate-induced delayed neuronal injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yonggang; Lein, Pamela J.; Liu, Cuimei

2012-07-15

Current medical countermeasures against organophosphate (OP) nerve agents are effective in reducing mortality, but do not sufficiently protect the CNS from delayed brain damage and persistent neurological symptoms. In this study, we examined the efficacy of neuregulin-1 (NRG-1) in protecting against delayed neuronal cell death following acute intoxication with the OP diisopropylflurophosphate (DFP). Adult male Sprague–Dawley rats were pretreated with pyridostigmine (0.1 mg/kg BW, i.m.) and atropine methylnitrate (20 mg/kg BW, i.m.) prior to DFP (9 mg/kg BW, i.p.) intoxication to increase survival and reduce peripheral signs of cholinergic toxicity but not prevent DFP-induced seizures or delayed neuronal injury. Pretreatmentmore » with NRG-1 did not protect against seizures in rats exposed to DFP. However, neuronal injury was significantly reduced in most brain regions by pretreatment with NRG-1 isoforms NRG-EGF (3.2 μg/kg BW, i.a) or NRG-GGF2 (48 μg/kg BW, i.a.) as determined by FluroJade-B labeling in multiple brain regions at 24 h post-DFP injection. NRG-1 also blocked apoptosis and oxidative stress-mediated protein damage in the brains of DFP-intoxicated rats. Administration of NRG-1 at 1 h after DFP injection similarly provided significant neuroprotection against delayed neuronal injury. These findings identify NRG-1 as a promising adjuvant therapy to current medical countermeasures for enhancing neuroprotection against acute OP intoxication. -- Highlights: ► NRG-1 blocked DFP induced neuronal injury. ► NRG-1 did not protect against seizures in rats exposed to DFP. ► NRG-1 blocked apoptosis and oxidative stress in the brains of DFP-intoxicated rats. ► Administration of NRG-1 at 1 h after DFP injection prevented delayed neuronal injury.« less

Relation of polymorphism of arsenic metabolism genes to arsenic methylation capacity and developmental delay in preschool children in Taiwan.

PubMed

Hsieh, Ru-Lan; Su, Chien-Tien; Shiue, Horng-Sheng; Chen, Wei-Jen; Huang, Shiau-Rung; Lin, Ying-Chin; Lin, Ming-I; Mu, Shu-Chi; Chen, Ray-Jade; Hsueh, Yu-Mei

2017-04-15

Inefficient arsenic methylation capacity has been associated with developmental delay in children. The present study was designed to explore whether polymorphisms and haplotypes of arsenic methyltransferase (AS3MT), glutathione-S-transferase omegas (GSTOs), and purine nucleoside phosphorylase (PNP) affect arsenic methylation capacity and developmental delay. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 179 children with developmental delay and 88 children without delay were recruited. Urinary arsenic species, including arsenite (As III ), arsenate (As V ), monomethylarsonic acid (MMA V ), and dimethylarsinic acid (DMA V ) were measured using a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphisms of AS3MT, GSTO, and PNP were performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Polymorphisms of AS3MT genes were found to affect susceptibility to developmental delay in children, but GSTO and PNP polymorphisms were not. Participants with AS3MT rs3740392 A/G+G/G genotype, compared with AS3MT rs3740392 A/A genotype, had a significantly lower secondary methylation index. This may result in an increased OR for developmental delay. Participants with the AS3MT high-risk haplotype had a significantly higher OR than those with AS3MT low-risk haplotypes [OR and 95% CI, 1.59 (1.08-2.34)]. This is the first study to show a joint dose-response effect of this AS3MT high-risk haplotype and inefficient arsenic methylation capacity on developmental delay. Our data provide evidence that AS3MT genes are related to developmental delay and may partially influence arsenic methylation capacity. Copyright © 2017 Elsevier Inc. All rights reserved.

Donnie-Boy

ERIC Educational Resources Information Center

Henderson, Mary

1974-01-01

The mother of a 21-year-old mentally retarded boy, who also suffers from frequent petit mal seizures, describes the developmental and behavioral problems which led her to seek institutional placement. (LH)

A Direct Comparison of Self-Injurious and Stereotyped Motor Behavior Between Preschool-Aged Children With and Without Developmental Delays.

PubMed

Hoch, John; Spofford, Lisa; Dimian, Adele; Tervo, Raymond; MacLean, William E; Symons, Frank J

2016-06-01

To compare the prevalence of self-injurious behavior (SIB) and stereotyped motor behavior (STY) of preschool-aged children with developmental delays (DD group) and their peers without developmental delays (TD group) using a standardized caregiver report scale. The Repetitive Behavior Scale-Revised was completed by caregivers of children with developmental delays and their peers without developmental delays. Frequency of occurrence and severity ratings for SIB and STY were compared between groups. SIB and STY were reported more often and at a greater level of severity in the DD group. Older chronological age was associated with more severe STY in the DD group but not the TD group. Gender was not related to STY or SIB for either group. Differences in STY and SIB were evident between preschoolers with and without DD. Findings are discussed from developmental and behavioral psychology perspectives regarding the expression of repetitive behavior in developmentally at-risk pediatric populations. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Supporting Optimal Neurodevelopmental Outcomes in Infants and Children With Congenital Heart Disease.

PubMed

Peterson, Jennifer K

2018-06-01

Improved survival has led to increased recognition of developmental delays in infants and children with congenital heart disease. Risk factors for developmental delays in congenital heart disease survivors may not be modifiable; therefore, it is important that lifesaving, high-technology critical care interventions be combined with nursing interventions that are also developmentally supportive. Implementing developmental care in a pediatric cardiac intensive care unit requires change implementation strategies and widespread support from all levels of health care professionals. This manuscript reviews developmentally supportive interventions such as massage, developmentally supportive positioning, kangaroo care, cue-based feeding, effective pain/anxiety management, and procedural preparation and identifies strategies to implement developmentally supportive interventions in the care of infants and children with congenital heart disease. Improving developmental support for these infants and children at high risk for developmental delay may improve their outcomes and help promote family-centered care. ©2018 American Association of Critical-Care Nurses.

The ketogenic diet is effective for refractory epilepsy associated with acquired structural epileptic encephalopathy.

PubMed

Villaluz, Mel Michel; Lomax, Lysa Boissé; Jadhav, Trupti; Cross, J Helen; Scheffer, Ingrid E

2018-07-01

Ketogenic diet therapies have proven efficacy for refractory epilepsy. There are many reports of their use in the genetic developmental and epileptic encephalopathies; however, little attention has been paid as to whether the diet is also effective in individuals with an acquired structural aetiology. We observed remarkable efficacy of the diet in two patients with hypoxic-ischaemic encephalopathy. We then analysed our cases with refractory structural epilepsies of acquired origin to characterize their response to the ketogenic diet. The classical ketogenic diet was implemented with dietary ratios of 3:1 to 4.4:1. Seizure frequency at 1 month, 3 months, 6 months, 1 year, and 2 years was ascertained. A responder was defined as greater than 50% seizure reduction compared to baseline. Seven of the nine patients were responders at 3 months. Somewhat surprisingly we found that the ketogenic diet was effective in patients with a developmental and epileptic encephalopathy due to an acquired structural aetiology. This cohort may not be routinely considered for the ketogenic diet because of their structural and acquired, rather than genetic, basis. The ketogenic diet should be considered early in the management of patients with acquired structural encephalopathies as it can improve seizure control with the potential to improve developmental outcome. The ketogenic diet was effective in children with epilepsy associated with an acquired structural aetiology. © 2018 Mac Keith Press.

Pre-school children with and without developmental delay: behaviour problems and parenting stress over time.

PubMed

Baker, B L; McIntyre, L L; Blacher, J; Crnic, K; Edelbrock, C; Low, C

2003-01-01

Children with intellectual disability are at heightened risk for behaviour problems and diagnosed mental disorder. The present authors studied the early manifestation and continuity of problem behaviours in 205 pre-school children with and without developmental delays. Behaviour problems were quite stable over the year from age 36-48 months. Children with developmental delays were rated higher on behaviour problems than their non-delayed peers, and were three times as likely to score in the clinical range. Mothers and fathers showed high agreement in their rating of child problems, especially in the delayed group. Parenting stress was also higher in the delayed group, but was related to the extent of behaviour problems rather than to the child's developmental delay. Over time, a transactional model fit the relationship between parenting stress and behaviour problems: high parenting stress contributed to a worsening in child behaviour problems over time, and high child behaviour problems contributed to a worsening in parenting stress. Findings for mothers and fathers were quite similar.

Pediatric epilepsy surgery: long-term 5-year seizure remission and medication use.

PubMed

Hauptman, Jason S; Pedram, Kayvon; Sison, Christia Angela; Sankar, Raman; Salamon, Noriko; Vinters, Harry V; Mathern, Gary W

2012-11-01

It is unclear whether long-term seizure outcomes in children are similar to those in adult epilepsy surgery patients. To determine 5-year outcomes and antiepilepsy drug (AED) use in pediatric epilepsy surgery patients from a single institution. The cohort consisted of children younger than 18 years of age whose 5-year outcome data would have been available by 2010. Comparisons were made between patients with and without 5-year data (n = 338), patients with 5-year data for seizure outcome (n = 257), and seizure-free patients on and off AEDs (n = 137). Five-year data were available from 76% of patients. More seizure-free patients with focal resections for hippocampal sclerosis and tumors lacked 5-year data compared with other cases. Of those with 5-year data, 53% were continuously seizure free, 18% had late seizure recurrence, 3% became seizure free after initial failure, and 25% were never seizure free. Patients were more likely to be continuously seizure free if their surgery was performed during the period 2001 to 2005 (68%) compared with surgery performed from 1996 to 2000 (61%), 1991 to 1995 (36%), and 1986 to 1990 (46%). More patients had 1 or fewer seizures per month in the late seizure recurrence (47%) compared with the not seizure-free group (20%). Four late deaths occurred in the not seizure-free group compared with 1 in the seizure-free group. Of patients who were continuously seizure free, 55% were not taking AEDs, and more cortical dysplasia patients (74%) had stopped taking AEDs compared with hemimegalencephaly patients (18%). In children, 5-year outcomes improved over 20 years of clinical experience. Our results are similar to those of adult epilepsy surgery patients despite mostly extratemporal and hemispheric operations for diverse developmental etiologies.

Down-regulation of delayed rectifier K+ channels in the hippocampus of seizure sensitive gerbils.

PubMed

Lee, Sang-Moo; Kim, Ji-Eun; Sohn, Jong-Hee; Choi, Hui-Chul; Lee, Ju-Sang; Kim, Sung-Hun; Kim, Min-Ju; Choi, Ihn-Geun; Kang, Tae-Cheon

2009-12-16

In order to confirm the species-specific distribution of voltage-gated K(+) (Kv) channels and the definitive relationship between their immunoreactivities and seizure activity, we investigated Kv2.x, Kv3.x and Kv4.x channel immunoreactivities in the hippocampi of seizure-resistant (SR) and seizure-sensitive (SS) gerbils. There was no difference in Kv2.1, Kv3.4, Kv4.2 and Kv4.3 immunoreactivity in the hippocampus between SR and SS gerbils. In comparison to SR gerbils, Kv3.1b immunoreactivity in neurons was significantly lower in SS gerbils instead Kv3.1b-immunoreactive astrocytes were clearly observed in SS gerbils (p<0.05). Kv3.2 immunoreactivity was also significantly lower in neurons of SS gerbils than in those of SR gerbils (p<0.05). Considering the findings of our previous study, these findings suggest that delayed rectifier K(+) channels (Kv1.1, Kv1.2, Kv1.5, Kv1.6, Kv2.1 and Kv3.1-2), not A-type K(+) channels (Kv1.4, Kv3.4 and Kv4.x), may be down-regulated in the SS gerbil hippocampus, as compared to SR gerbils.

Self-Recognition in Young Children Using Delayed versus Live Feedback: Evidence of a Developmental Asynchrony.

ERIC Educational Resources Information Center

Povinelli, Daniel J.; And Others

1996-01-01

Investigated the ability of young children to recognize themselves in delayed videotapes and recent photographs. Results suggested a significant developmental delay in young children's success on mark tests of self-recognition using delayed feedback as compared to live feedback, which may have important implications for characterizing the…

Neonatal seizures triple the risk of a remote seizure after perinatal ischemic stroke.

PubMed

Fox, Christine K; Glass, Hannah C; Sidney, Stephen; Smith, Sabrina E; Fullerton, Heather J

2016-06-07

To determine incidence rates and risk factors of remote seizure after perinatal arterial ischemic stroke. We retrospectively identified a population-based cohort of children with perinatal arterial ischemic stroke (presenting acutely or in a delayed fashion) from a large Northern Californian integrated health care system. We determined incidence and predictors of a remote seizure (unprovoked seizure after neonatal period, defined as 28 days of life) by survival analyses, and measured epilepsy severity in those with active epilepsy (≥1 remote seizure and maintenance anticonvulsant treatment) at last follow-up. Among 87 children with perinatal stroke, 40 (46%) had a seizure in the neonatal period. During a median follow-up of 7.1 years (interquartile range 3.2-10.5), 37 children had ≥1 remote seizure. Remote seizure risk was highest during the first year of life, with a 20% (95% confidence interval [CI] 13%-30%) cumulative incidence by 1 year of age, 46% (CI 35%-58%) by 5 years, and 54% (CI 41%-67%) by 10 years. Neonatal seizures increased the risk of a remote seizure (hazard ratio 2.8, CI 1.3-5.8). Children with neonatal seizures had a 69% (CI 48%-87%) cumulative incidence of remote seizure by age 10 years. Among the 24 children with active epilepsy at last follow-up, 8 (33%) were having monthly seizures despite an anticonvulsant and 7 (29%) were on more than one anticonvulsant. Remote seizures and epilepsy, including medically refractory epilepsy, are common after perinatal stroke. Neonatal seizures are associated with nearly 3-fold increased remote seizure risk. © 2016 American Academy of Neurology.

Evaluation of the Affymetrix CytoScan® Dx Assay for Developmental Delay

PubMed Central

Webb, Bryn D.; Scharf, Rebecca J.; Spear, Emily A.; Edelmann, Lisa J.; Stroustrup, Annemarie

2015-01-01

The goal of molecular cytogenetic testing for children presenting with developmental delay is to identify or exclude genetic abnormalities that are associated with cognitive, behavioral, and/or motor symptoms. Until 2010, chromosome analysis was the standard first-line genetic screening test for evaluation of patients with developmental delay when a specific syndrome was not suspected. In 2010, The American College of Medical Genetics and several other groups recommended chromosomal microarray (CMA) as the first-line test in children with developmental delays, multiple congenital anomalies, and/or autism. This test is able to detect regions of genomic imbalances at a much finer resolution than G-banded karyotyping. Until recently, no CMA testing had been approved by the United States Food and Drug Administration (FDA). This review will focus on the use of the Affymetrix CytoScan® Dx Assay, the first CMA to receive FDA approval for the genetic evaluation of individuals with developmental delay. PMID:25350348

Carer Reports of Health Status among Adults with Intellectual/Developmental Disabilities in Taiwan Living at Home and in Institutions

ERIC Educational Resources Information Center

Wang, K.-Y.; Hsieh, K.; Heller, T.; Davidson, P. W.; Janicki, M. P.

2007-01-01

Background: The aim of the present study was to assess the health status of a cohort of adults with intellectual/developmental disabilities (I/DD) residing in family homes or institutions in Taiwan and to examine whether morbidity varied with age, sex, existing diagnosis [Down syndrome (DS), seizures, cerebral palsy (CP), intellectual disability…

Enduring Memory Impairments Provoked by Developmental Febrile Seizures Are Mediated by Functional and Structural Effects of Neuronal Restrictive Silencing Factor

PubMed Central

Patterson, Katelin P.; Barry, Jeremy M.; Singh-Taylor, Akanksha; Brennan, Gary; Page, Matias; Holmes, Gregory L.

2017-01-01

In a subset of children experiencing prolonged febrile seizures (FSs), the most common type of childhood seizures, cognitive outcomes are compromised. However, the underlying mechanisms are unknown. Here we identified significant, enduring spatial memory problems in male rats following experimental prolonged FS (febrile status epilepticus; eFSE). Remarkably, these deficits were abolished by transient, post hoc interference with the chromatin binding of the transcriptional repressor neuron restrictive silencing factor (NRSF or REST). This transcriptional regulator is known to contribute to neuronal differentiation during development and to programmed gene expression in mature neurons. The mechanisms of the eFSE-provoked memory problems involved complex disruption of memory-related hippocampal oscillations recorded from CA1, likely resulting in part from impairments of dendritic filtering of cortical inputs as well as abnormal synaptic function. Accordingly, eFSE provoked region-specific dendritic loss in the hippocampus, and aberrant generation of excitatory synapses in dentate gyrus granule cells. Blocking NRSF transiently after eFSE prevented granule cell dysmaturation, restored a functional balance of γ-band network oscillations, and allowed treated eFSE rats to encode and retrieve spatial memories. Together, these studies provide novel insights into developing networks that underlie memory, the mechanisms by which early-life seizures influence them, and the means to abrogate the ensuing cognitive problems. SIGNIFICANCE STATEMENT Whereas seizures have been the central focus of epilepsy research, they are commonly accompanied by cognitive problems, including memory impairments that contribute to poor quality of life. These deficits often arise before the onset of spontaneous seizures, or independent from them, yet the mechanisms involved are unclear. Here, using a rodent model of common developmental seizures that provoke epilepsy in a subset of individuals, we identify serious consequent memory problems. We uncover molecular, cellular, and circuit-level mechanisms that underlie these deficits and successfully abolish them by targeted therapeutic interventions. These findings may be important for understanding and preventing cognitive problems in individuals suffering long febrile seizures. PMID:28275159

Enduring Memory Impairments Provoked by Developmental Febrile Seizures Are Mediated by Functional and Structural Effects of Neuronal Restrictive Silencing Factor.

PubMed

Patterson, Katelin P; Barry, Jeremy M; Curran, Megan M; Singh-Taylor, Akanksha; Brennan, Gary; Rismanchi, Neggy; Page, Matias; Noam, Yoav; Holmes, Gregory L; Baram, Tallie Z

2017-04-05

In a subset of children experiencing prolonged febrile seizures (FSs), the most common type of childhood seizures, cognitive outcomes are compromised. However, the underlying mechanisms are unknown. Here we identified significant, enduring spatial memory problems in male rats following experimental prolonged FS (febrile status epilepticus; eFSE). Remarkably, these deficits were abolished by transient, post hoc interference with the chromatin binding of the transcriptional repressor neuron restrictive silencing factor (NRSF or REST). This transcriptional regulator is known to contribute to neuronal differentiation during development and to programmed gene expression in mature neurons. The mechanisms of the eFSE-provoked memory problems involved complex disruption of memory-related hippocampal oscillations recorded from CA1, likely resulting in part from impairments of dendritic filtering of cortical inputs as well as abnormal synaptic function. Accordingly, eFSE provoked region-specific dendritic loss in the hippocampus, and aberrant generation of excitatory synapses in dentate gyrus granule cells. Blocking NRSF transiently after eFSE prevented granule cell dysmaturation, restored a functional balance of γ-band network oscillations, and allowed treated eFSE rats to encode and retrieve spatial memories. Together, these studies provide novel insights into developing networks that underlie memory, the mechanisms by which early-life seizures influence them, and the means to abrogate the ensuing cognitive problems. SIGNIFICANCE STATEMENT Whereas seizures have been the central focus of epilepsy research, they are commonly accompanied by cognitive problems, including memory impairments that contribute to poor quality of life. These deficits often arise before the onset of spontaneous seizures, or independent from them, yet the mechanisms involved are unclear. Here, using a rodent model of common developmental seizures that provoke epilepsy in a subset of individuals, we identify serious consequent memory problems. We uncover molecular, cellular, and circuit-level mechanisms that underlie these deficits and successfully abolish them by targeted therapeutic interventions. These findings may be important for understanding and preventing cognitive problems in individuals suffering long febrile seizures. Copyright © 2017 the authors 0270-6474/17/373799-14$15.00/0.

Treatment Trials for Neonatal Seizures: The Effect of Design on Sample Size

PubMed Central

Stevenson, Nathan J.; Boylan, Geraldine B.; Hellström-Westas, Lena; Vanhatalo, Sampsa

2016-01-01

Neonatal seizures are common in the neonatal intensive care unit. Clinicians treat these seizures with several anti-epileptic drugs (AEDs) to reduce seizures in a neonate. Current AEDs exhibit sub-optimal efficacy and several randomized control trials (RCT) of novel AEDs are planned. The aim of this study was to measure the influence of trial design on the required sample size of a RCT. We used seizure time courses from 41 term neonates with hypoxic ischaemic encephalopathy to build seizure treatment trial simulations. We used five outcome measures, three AED protocols, eight treatment delays from seizure onset (Td) and four levels of trial AED efficacy to simulate different RCTs. We performed power calculations for each RCT design and analysed the resultant sample size. We also assessed the rate of false positives, or placebo effect, in typical uncontrolled studies. We found that the false positive rate ranged from 5 to 85% of patients depending on RCT design. For controlled trials, the choice of outcome measure had the largest effect on sample size with median differences of 30.7 fold (IQR: 13.7–40.0) across a range of AED protocols, Td and trial AED efficacy (p<0.001). RCTs that compared the trial AED with positive controls required sample sizes with a median fold increase of 3.2 (IQR: 1.9–11.9; p<0.001). Delays in AED administration from seizure onset also increased the required sample size 2.1 fold (IQR: 1.7–2.9; p<0.001). Subgroup analysis showed that RCTs in neonates treated with hypothermia required a median fold increase in sample size of 2.6 (IQR: 2.4–3.0) compared to trials in normothermic neonates (p<0.001). These results show that RCT design has a profound influence on the required sample size. Trials that use a control group, appropriate outcome measure, and control for differences in Td between groups in analysis will be valid and minimise sample size. PMID:27824913

Oxygen desaturations triggered by partial seizures: implications for cardiopulmonary instability in epilepsy

NASA Technical Reports Server (NTRS)

Blum, A. S.; Ives, J. R.; Goldberger, A. L.; Al-Aweel, I. C.; Krishnamurthy, K. B.; Drislane, F. W.; Schomer, D. L.

2000-01-01

PURPOSE: The occurrence of hypoxemia in adults with partial seizures has not been systematically explored. Our aim was to study in detail the temporal dynamics of this specific type of ictal-associated hypoxemia. METHODS: During long-term video/EEG monitoring (LTM), patients underwent monitoring of oxygen saturation using a digital Spo2 (pulse oximeter) transducer. Six patients (nine seizures) were identified with oxygen desaturations after the onset of partial seizure activity. RESULTS: Complex partial seizures originated from both left and right temporal lobes. Mean seizure duration (+/-SD) was 73 +/- 18 s. Mean Spo2 desaturation duration was 76 +/- 19 s. The onset of oxygen desaturation followed seizure onset with a mean delay of 43 +/- 16 s. Mean (+/-SD) Spo2 nadir was 83 +/- 5% (range, 77-91%), occurring an average of 35 +/- 12 s after the onset of the desaturation. One seizure was associated with prolonged and recurrent Spo2 desaturations. CONCLUSIONS: Partial seizures may be associated with prominent oxygen desaturations. The comparable duration of each seizure and its subsequent desaturation suggests a close mechanistic (possibly causal) relation. Spo2 monitoring provides an added means for seizure detection that may increase LTM yield. These observations also raise the possibility that ictal ventilatory dysfunction could play a role in certain cases of sudden unexpected death in epilepsy in adults with partial seizures.

Immune-mediated steroid-responsive epileptic spasms and epileptic encephalopathy associated with VGKC-complex antibodies.

PubMed

Suleiman, Jehan; Brenner, Tanja; Gill, Deepak; Troedson, Christopher; Sinclair, Adriane J; Brilot, Fabienne; Vincent, Angela; Lang, Bethan; Dale, Russell C

2011-11-01

Autoantibodies that bind to voltage-gated potassium-channel complex proteins (VGKC-complex antibodies) occur frequently in adults with limbic encephalitis presenting with cognitive impairment and seizures. Recently, VGKC-complex antibodies have been described in a few children with limbic encephalitis, and children with unexplained encephalitis presenting with status epilepticus. We report a case of infantile-onset epileptic spasms and developmental delay compatible with epileptic encephalopathy. Our patient was a female infant, aged 4 months at presentation. She had evidence of immune activation in the central nervous system with elevated cerebrospinal fluid neopterin and mirrored oligoclonal bands, which prompted testing for autoantibodies. VGKC-complex antibodies were elevated (201 pmol/L, normal<100), but extended antibody testing, including leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2), was negative. The patient showed a partial response to steroid treatment, which was started late in the disease course. On review at 13 months of age, her development was consistent with an age of 5 to 6 months. These results suggest that VGKC-complex antibodies might represent a marker of immune therapy responsiveness in a subgroup of patients with infantile epileptic encephalopathy. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

Ventral pallidum deep brain stimulation attenuates acute partial, generalized and tonic-clonic seizures in two rat models.

PubMed

Mahoney, Emily C; Zeng, Andrew; Yu, Wilson; Rowe, Mackenzie; Sahai, Siddhartha; Feustel, Paul J; Ramirez-Zamora, Adolfo; Pilitsis, Julie G; Shin, Damian S

2018-05-01

Approximately 30% of individuals with epilepsy are refractory to antiepileptic drugs and currently approved neuromodulatory approaches fall short of providing seizure freedom for many individuals with limited utility for generalized seizures. Here, we expand on previous findings and investigate whether ventral pallidum deep brain stimulation (VP-DBS) can be efficacious for various acute seizure phenotypes. For rats administered pilocarpine, we found that VP-DBS (50 Hz) decreased generalized stage 4/5 seizure median frequency from 9 to 6 and total duration from 1667 to 264 s even after generalized seizures emerged. The transition to brainstem seizures was prevented in almost all animals. VP-DBS immediately after rats exhibited their first partial forebrain stage 3 seizure did not affect the frequency of partial seizures but reduced median partial seizure duration from 271 to 54 s. Stimulation after partial seizures also reduced the occurrence and duration of secondarily generalized stage 4/5 seizures. VP-DBS prior to pilocarpine administration prevented the appearance of partial seizures in almost all animals. Lastly, VP-DBS delayed the onset of generalized tonic-clonic seizures (GTCSs) from 111 to 823 s in rats administered another chemoconvulsant, pentylenetetrazol (PTZ, 90 mg/kg). In this particular rat seizure model, stimulating electrodes placed more laterally in both VP hemispheres and more posterior in the left VP hemisphere provided greatest efficacy for GTCSs. In conclusion, our findings posit that VP-DBS can serve as an effective novel neuromodulatory approach for a variety of acute seizure phenotypes. Copyright © 2018 Elsevier B.V. All rights reserved.

Decreased head circumference velocity as related to developmental deficit in infancy.

PubMed

Tal, Galit; Cohen, Ayala; Habib, Sonia; Tirosh, Emanuel

2012-11-01

We evaluated the significance of head circumference growth velocity as related to developmental deficits during infancy. Head circumferences, lengths, and developmental diagnoses were retrieved in a standard manner at ≥ 2 time points from 437 infants with developmental deficits, and 3909 normally developing infants. Infants' ages ranged from 1-24 months, with final diagnoses ascertained at age 24 months. Increased velocity during the first 2 months in typical infants was evident in the study group during the period 2-4 months. A differential head circumference growth velocity was observed, and infants diagnosed with motor delay presented decreased velocity between ages 2-4 months, compared with infants receiving other nonmotor developmental diagnoses. These differences remained after controlling for birth weight and length. No significant sex effect was evident. Infants with developmental deficits demonstrate delayed acceleration of head circumference velocity, compared with typical infants in the first 2 months. Infants with motor delay manifest decreased velocity, compared with infants presenting other developmental deficits. These differences may be related to delayed white matter maturation. Copyright © 2012 Elsevier Inc. All rights reserved.

Mutations in KPTN Cause Macrocephaly, Neurodevelopmental Delay, and Seizures

PubMed Central

Baple, Emma L.; Maroofian, Reza; Chioza, Barry A.; Izadi, Maryam; Cross, Harold E.; Al-Turki, Saeed; Barwick, Katy; Skrzypiec, Anna; Pawlak, Robert; Wagner, Karin; Coblentz, Roselyn; Zainy, Tala; Patton, Michael A.; Mansour, Sahar; Rich, Phillip; Qualmann, Britta; Hurles, Matt E.; Kessels, Michael M.; Crosby, Andrew H.

2014-01-01

The proper development of neuronal circuits during neuromorphogenesis and neuronal-network formation is critically dependent on a coordinated and intricate series of molecular and cellular cues and responses. Although the cortical actin cytoskeleton is known to play a key role in neuromorphogenesis, relatively little is known about the specific molecules important for this process. Using linkage analysis and whole-exome sequencing on samples from families from the Amish community of Ohio, we have demonstrated that mutations in KPTN, encoding kaptin, cause a syndrome typified by macrocephaly, neurodevelopmental delay, and seizures. Our immunofluorescence analyses in primary neuronal cell cultures showed that endogenous and GFP-tagged kaptin associates with dynamic actin cytoskeletal structures and that this association is lost upon introduction of the identified mutations. Taken together, our studies have identified kaptin alterations responsible for macrocephaly and neurodevelopmental delay and define kaptin as a molecule crucial for normal human neuromorphogenesis. PMID:24239382

Developmental risk and young children's regulatory strategies: predicting behavior problems at age five.

PubMed

Gerstein, Emily D; Pedersen Y Arbona, Anita; Crnic, Keith A; Ryu, Ehri; Baker, Bruce L; Blacher, Jan

2011-04-01

Children with early developmental delays are at heightened risk for behavior problems and comorbid psychopathology. This study examined the trajectories of regulatory capabilities and their potentially mediating role in the development of behavior problems for children with and without early developmental delays. A sample of 231 children comprised of 137 typically developing children and 94 children with developmental delays were examined during mildly frustrating laboratory tasks across the preschool period (ages 3-5). Results indicated that children with delays had greater use of maladaptive strategies (distraction, distress venting) and lower use of adaptive strategies (constructive coping) than typically developing children. For both groups, strategies had similar rates of growth across time; maladaptive strategies decreased and adaptive strategies increased. The intercept of strategy use, but not the slope, was found to mediate the relation between developmental risk and externalizing behaviors. Findings support that dysregulation, rather than the developmental risk, may be responsible for the high levels of comorbid psychopathology.

Neurocognitive, Social-Behavioral, and Adaptive Functioning in Preschool Children with Mild to Moderate Kidney Disease

PubMed Central

Hooper, Stephen R.; Gerson, Arlene C.; Johnson, Rebecca J.; Mendley, Susan R.; Shinnar, Shlomo; Lande, Marc B.; Matheson, Matthew B.; Gipson, Debbie S.; Morgenstern, Bruce; Warady, Bradley A.; Furth, Susan L.

2016-01-01

Objective The negative impact of End Stage Kidney Disease on cognitive function in children is well established, but no studies have examined the neurocognitive, social-behavioral, and adaptive behavior skills of preschool children with mild to moderate chronic kidney disease (CKD). Methods Participants included 124 preschool children with mild to moderate CKD, ages 12-68 months (median=3.7 years), and an associated mean glomerular filtration rate (GFR) of 50.0 ml/min per 1.73m2. In addition to level of function and percent of participants scoring≥1SD below the test mean, regression models examined the associations between biomarkers of CKD (GFR, anemia, hypertension, seizures, abnormal birth history), and Developmental Level/IQ, attention regulation, and parent ratings of executive functions, social-behavior, and adaptive behaviors. Results Median scores for all measures were in the average range; however, 27% were deemed at-risk for a Developmental Level/IQ<85, 20% were at-risk for attention variability, and parent ratings indicated 30% and 37% to be at-risk for executive dysfunction and adaptive behavior problems, respectively. Approximately 43% were deemed at-risk on two or more measures. None of the disease-related variables were significantly associated with these outcomes, although the presence of hypertension approached significance for attention variability (p<.09). Abnormal birth history and lower maternal education were significantly related to lower Developmental Level/IQ; seizures were related to lower parental ratings of executive function and adaptive behavior; and abnormal birth history was significantly related to lower ratings of adaptive behavior. When predicting risk status, the logistic regression did evidence both higher GFR and the lack of anemia to be associated with more intact Developmental Level/IQ. Conclusions These findings suggest relatively intact functioning for preschool children with mild to moderate CKD, but the need for ongoing developmental surveillance in this population remains warranted, particularly for those with abnormal birth histories, seizures, and heightened disease severity. PMID:26890559

Small rare recurrent deletions and reciprocal duplications in 2q21.1, including brain-specific ARHGEF4 and GPR148

PubMed Central

Dharmadhikari, Avinash V.; Kang, Sung-Hae L.; Szafranski, Przemyslaw; Person, Richard E.; Sampath, Srirangan; Prakash, Siddharth K.; Bader, Patricia I.; Phillips, John A.; Hannig, Vickie; Williams, Misti; Vinson, Sherry S.; Wilfong, Angus A.; Reimschisel, Tyler E.; Craigen, William J.; Patel, Ankita; Bi, Weimin; Lupski, James R.; Belmont, John; Cheung, Sau Wai; Stankiewicz, Pawel

2012-01-01

We have identified a rare small (∼450 kb unique sequence) recurrent deletion in a previously linked attention-deficit hyperactivity disorder (ADHD) locus at 2q21.1 in five unrelated families with developmental delay (DD)/intellectual disability (ID), ADHD, epilepsy and other neurobehavioral abnormalities from 17 035 samples referred for clinical chromosomal microarray analysis. Additionally, a DECIPHER (http://decipher.sanger.ac.uk) patient 2311 was found to have the same deletion and presented with aggressive behavior. The deletion was not found in either six control groups consisting of 13 999 healthy individuals or in the DGV database. We have also identified reciprocal duplications in five unrelated families with autism, developmental delay (DD), seizures and ADHD. This genomic region is flanked by large, complex low-copy repeats (LCRs) with directly oriented subunits of ∼109 kb in size that have 97.7% DNA sequence identity. We sequenced the deletion breakpoints within the directly oriented paralogous subunits of the flanking LCR clusters, demonstrating non-allelic homologous recombination as a mechanism of formation. The rearranged segment harbors five genes: GPR148, FAM123C, ARHGEF4, FAM168B and PLEKHB2. Expression of ARHGEF4 (Rho guanine nucleotide exchange factor 4) is restricted to the brain and may regulate the actin cytoskeletal network, cell morphology and migration, and neuronal function. GPR148 encodes a G-protein-coupled receptor protein expressed in the brain and testes. We suggest that small rare recurrent deletion of 2q21.1 is pathogenic for DD/ID, ADHD, epilepsy and other neurobehavioral abnormalities and, because of its small size, low frequency and more severe phenotype might have been missed in other previous genome-wide screening studies using single-nucleotide polymorphism analyses. PMID:22543972

Uric acid, an important screening tool to detect inborn errors of metabolism: a case series.

PubMed

Jasinge, Eresha; Kularatnam, Grace Angeline Malarnangai; Dilanthi, Hewa Warawitage; Vidanapathirana, Dinesha Maduri; Jayasena, Kandana Liyanage Subhashinie Priyadarshika Kapilani Menike; Chandrasiri, Nambage Dona Priyani Dhammika; Indika, Neluwa Liyanage Ruwan; Ratnayake, Pyara Dilani; Gunasekara, Vindya Nandani; Fairbanks, Lynette Dianne; Stiburkova, Blanka

2017-09-06

Uric acid is the metabolic end product of purine metabolism in humans. Altered serum and urine uric acid level (both above and below the reference ranges) is an indispensable marker in detecting rare inborn errors of metabolism. We describe different case scenarios of 4 Sri Lankan patients related to abnormal uric acid levels in blood and urine. CASE 1: A one-and-half-year-old boy was investigated for haematuria and a calculus in the bladder. Xanthine crystals were seen in microscopic examination of urine sediment. Low uric acid concentrations in serum and low urinary fractional excretion of uric acid associated with high urinary excretion of xanthine and hypoxanthine were compatible with xanthine oxidase deficiency. CASE 2: An 8-month-old boy presented with intractable seizures, feeding difficulties, screaming episodes, microcephaly, facial dysmorphism and severe neuro developmental delay. Low uric acid level in serum, low fractional excretion of uric acid and radiological findings were consistent with possible molybdenum cofactor deficiency. Diagnosis was confirmed by elevated levels of xanthine, hypoxanthine and sulfocysteine levels in urine. CASE 3: A 3-year-10-month-old boy presented with global developmental delay, failure to thrive, dystonia and self-destructive behaviour. High uric acid levels in serum, increased fractional excretion of uric acid and absent hypoxanthine-guanine phosphoribosyltransferase enzyme level confirmed the diagnosis of Lesch-Nyhan syndrome. CASE 4: A 9-year-old boy was investigated for lower abdominal pain, gross haematuria and right renal calculus. Low uric acid level in serum and increased fractional excretion of uric acid pointed towards hereditary renal hypouricaemia which was confirmed by genetic studies. Abnormal uric acid level in blood and urine is a valuable tool in screening for clinical conditions related to derangement of the nucleic acid metabolic pathway.

Febrile Seizures and Epilepsy: Association With Autism and Other Neurodevelopmental Disorders in the Child and Adolescent Twin Study in Sweden.

PubMed

Gillberg, Christopher; Lundström, Sebastian; Fernell, Elisabeth; Nilsson, Gill; Neville, Brian

2017-09-01

There is a recently well-documented association between childhood epilepsy and earlysymptomaticsyndromeselicitingneurodevelopmentalclinicalexaminations (ESSENCE) including autism spectrum disorder, but the relationship between febrile seizures and ESSENCE is less clear. The Child and Adolescent Twin Study in Sweden (CATSS) is an ongoing population-based study targeting twins born in Sweden since July 1, 1992. Parents of 27,092 twins were interviewed using a validated DSM-IV-based interview for ESSENCE, in connection with the twins' ninth or twelfth birthday. Diagnoses of febrile seizures (n = 492) and epilepsy (n = 282) were based on data from the Swedish National Patient Register. Prevalence of ESSENCE in individuals with febrile seizures and epilepsy was compared with prevalence in the twin population without seizures. The association between febrile seizures and ESSENCE was considered before and after adjustment for epilepsy. Age of diagnosis of febrile seizures and epilepsy was considered as a possible correlate of ESSENCE in febrile seizures and epilepsy. The rate of ESSENCE in febrile seizures and epilepsy was significantly higher than in the total population without seizures (all P < 0.001). After adjusting for epilepsy, a significant association between febrile seizures and autism spectrum disorder, developmental coordination disorder, and intellectual disability remained. Earlier age of onset was associated with all ESSENCE except attention-deficit/hyperactivity disorder in epilepsy but not with ESSENCE in febrile seizures. In a nationally representative sample of twins, there was an increased rate of ESSENCE in childhood epilepsy and in febrile seizures. Febrile seizures alone could occur as a marker for a broader ESSENCE phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.

Developmental delay in the Amazon: The social determinants and prevalence among rural communities in Peru

PubMed Central

Alnasser, Yossef

2017-01-01

The consequences of poor child development are becoming increasingly recognized. Programs are being put in place around the world to improve child development by providing healthy and stimulating environments for children. However, these programs often have limited reach and little is known about the prevalence of developmental delay in under-developed communities. The current study set-out to better understand the prevalence of developmental delay in rural communities in the Amazon region of Peru. Also, it explores social determinants that are associated with any delay. Cross-sectional study by evaluating developmental delay in children under 4 years utilizing Ages and Stages Questionnaire (ASQ-3). Additionally, conducting a social determinants questionnaire answered by caretakers to identify social drivers for developmental delay. The data was analyzed with multi-variant analysis to measure association. The prevalence of developmental delay in the Amazonian communities was 26.7% (19.3% in communication, 11.4% in gross motor skills, 8% in both) (N = 596). The multivariate logistic regression analysis revealed significant associations between developmental delay and; level of education (OR 0.64, p = 0.009), age of mother during child’s birth (OR 0.96, p = 0.002), visits by community health agents (OR 0.73, p = 0.013), and river as primary water source (OR 2.39, p = 0.001). The social determinants questionnaire revealed that 39% of the mothers had their first child before the age of 17, nearly half stopped going to school before the age of 12 (52%), 29% gave birth at home, 13% breast fed for less than 7 months, and 50% of the children had diarrhea in the last month. There is still a great need to improve the conditions for child development in the Amazon region of Peru. One-fourth of the children suffer from developmental delay, which will likely impede their potentials for life unless something is done. The impact of education, age of mother at birth of the child, community health agents, and access to clean drinking water were important findings. Improvements can be made in these areas to create a large, cost-effective impact on the well-being of the communities. PMID:29023517

Developmental delay in the Amazon: The social determinants and prevalence among rural communities in Peru.

PubMed

Westgard, Christopher; Alnasser, Yossef

2017-01-01

The consequences of poor child development are becoming increasingly recognized. Programs are being put in place around the world to improve child development by providing healthy and stimulating environments for children. However, these programs often have limited reach and little is known about the prevalence of developmental delay in under-developed communities. The current study set-out to better understand the prevalence of developmental delay in rural communities in the Amazon region of Peru. Also, it explores social determinants that are associated with any delay. Cross-sectional study by evaluating developmental delay in children under 4 years utilizing Ages and Stages Questionnaire (ASQ-3). Additionally, conducting a social determinants questionnaire answered by caretakers to identify social drivers for developmental delay. The data was analyzed with multi-variant analysis to measure association. The prevalence of developmental delay in the Amazonian communities was 26.7% (19.3% in communication, 11.4% in gross motor skills, 8% in both) (N = 596). The multivariate logistic regression analysis revealed significant associations between developmental delay and; level of education (OR 0.64, p = 0.009), age of mother during child's birth (OR 0.96, p = 0.002), visits by community health agents (OR 0.73, p = 0.013), and river as primary water source (OR 2.39, p = 0.001). The social determinants questionnaire revealed that 39% of the mothers had their first child before the age of 17, nearly half stopped going to school before the age of 12 (52%), 29% gave birth at home, 13% breast fed for less than 7 months, and 50% of the children had diarrhea in the last month. There is still a great need to improve the conditions for child development in the Amazon region of Peru. One-fourth of the children suffer from developmental delay, which will likely impede their potentials for life unless something is done. The impact of education, age of mother at birth of the child, community health agents, and access to clean drinking water were important findings. Improvements can be made in these areas to create a large, cost-effective impact on the well-being of the communities.

Earlier tachycardia onset in right than left mesial temporal lobe seizures.

PubMed

Kato, Kazuhiro; Jin, Kazutaka; Itabashi, Hisashi; Iwasaki, Masaki; Kakisaka, Yosuke; Aoki, Masashi; Nakasato, Nobukazu

2014-10-07

To clarify whether the presence and timing of peri-ictal heart rate (HR) change is a seizure lateralizing sign in patients with mesial temporal lobe epilepsy (mTLE). Long-term video EEGs were retrospectively reviewed in 21 patients, 7 men and 14 women aged 13 to 67 years, diagnosed as mTLE with MRI lesions in the mesial temporal structures (hippocampal sclerosis in 20 cases, amygdala hypertrophy in 1 case). Seventy-seven partial seizures without secondary generalization were extracted. Peri-ictal HR change was compared between 29 right seizures (9 patients) and 48 left seizures (12 patients). HR abruptly increased in all 29 right seizures and 42 of 48 left seizures. Onset time of HR increase in relation to ictal EEG onset was significantly earlier in right seizures than in left seizures (mean ± SD, -11.5 ± 14.8 vs 9.2 ± 21.7 seconds; p < 0.0001). Time of maximum HR was also significantly earlier in right seizures than in left seizures (36.0 ± 18.1 vs 58.0 ± 28.7 seconds; p < 0.0001). Maximum HR changes from baseline showed no significant difference between right and left seizures (47.5 ± 19.1 vs 40.8 ± 20.0/min). Significantly earlier tachycardia in right than left mTLE seizures supports previous hypotheses that the right cerebral hemisphere is dominant in the sympathetic network. No HR change, or delayed tachycardia possibly due to seizure propagation to the right hemisphere, may be a useful lateralizing sign of left mTLE seizures. © 2014 American Academy of Neurology.

Dcx Re-expression Reduces Subcortical Band Heterotopia and Seizure Threshold in an Animal Model of Neuronal Migration Disorder

PubMed Central

Manent, Jean-Bernard; Wang, Yu; Chang, YoonJeung; Paramasivam, Murugan; LoTurco, Joseph J

2009-01-01

Disorders of neuronal migration can lead to malformations of the cerebral neocortex that greatly increase the risk of seizures. It remains untested whether malformations caused by disorders in neuronal migration can be reduced by reactivating cellular migration, and whether such repair can decrease seizure risk. Here we show, in a rat model of subcortical band heterotopia (SBH) generated by in utero RNAi of Dcx, that aberrantly positioned neurons can be stimulated to migrate by re-expressing Dcx after birth. Re-starting migration in this way both reduces neocortical malformations and restores neuronal patterning. We find further that the capacity to reduce SBH has a critical period in early postnatal development. Moreover, intervention after birth reduces convulsant-induced seizure threshold to levels similar to that of malformation-free controls. These results suggest that disorders of neuronal migration may be eventually treatable by re-engaging developmental programs both to reduce the size of cortical malformations and to reduce seizure risk. PMID:19098909

Prenatal corticosteroid exposure alters early developmental seizures and behavior

PubMed Central

Velíšek, Libor

2011-01-01

In humans, corticosteroids are often administered prenatally to improve lung development in preterm neonates. Studies in exposed children as well as in children, whose mothers experienced significant stress during pregnancy indicate behavioral problems and possible increased occurrence of epileptic spasms. This study investigated whether prenatal corticosteroid exposure alters early postnatal seizure susceptibility and behaviors. On gestational day 15, pregnant rats were injected i.p. with hydrocortisone (2× 10 mg/kg), betamethasone (2× 0.4 mg/kg) or vehicle. On postnatal day (P)15, seizures were induced by flurothyl or kainic acid (3.5 or 5.0 mg/kg). Horizontal bar holding was determined prior to seizures and again on P17. Performance in the elevated plus maze was assessed on P20-22. Prenatal exposure to betamethasone decreased postnatal susceptibility to flurothyl-induced clonic seizures but not to kainic acid-induced seizures. Prenatal hydrocortisone decreased postnatal weight but did not affect seizure susceptibility. Hydrocortisone alone did not affect performance in behavioral tests except for improving horizontal bar holding on P17. A combination of prenatal hydrocortisone and postnatal seizures resulted in increased anxiety. Prenatal exposure to mineralocorticoid receptor blocker canrenoic acid did not attenuate, but surprisingly amplified the effects of hydrocortisone on body weight and significantly worsened horizontal bar performance. Thus, prenatal exposure to excess corticosteroids alters postnatal seizure susceptibility and behaviors. Specific effects may depend on corticosteroid species. PMID:21429712

Mild Wolf-Hirschhorn phenotype and partial GH deficiency in a patient with a 4p terminal deletion.

PubMed

Titomanlio, L; Romano, A; Conti, A; Genesio, R; Salerno, M; De Brasi, D; Nitsch, L; Del Giudice, E

2004-06-01

Wolf-Hirschhorn syndrome (WHS) is caused by a variably-sized deletion of chromosome 4 involving band 4p16 whose typical craniofacial features are "Greek warrior helmet appearance" of the nose, microcephaly, and prominent glabella. Almost all patients show mental retardation and pre- and post-natal growth delay. Patient was born at term, after a pregnancy characterized by intra-uterine growth retardation (IUGR). Delivery was uneventful. Developmental delay was evident since the first months of life. At 2 years, he developed generalized tonic-clonic seizures. Because of short stature, low growth velocity and delayed bone age, at 4 years he underwent growth hormone (GH) evaluation. Peak GH after two provocative tests revealed a partial GH deficiency. Clinical observation at 7 years disclosed a distinctive facial appearance, with microcephaly, prominent eyes, and beaked nose. Brain MRI showed left temporal mesial sclerosis. GTG banded karyotype was normal. Because of mental retardation, subtelomeric fluorescence in situ hybridization (FISH) analysis was performed, disclosing a relatively large deletion involving 4p16.2 --> pter (about 4.5 Mb), in the proband, not present in the parents. The smallest deletion detected in a WHS patient thus far includes two candidate genes, WHSC1 and WHSC2. Interestingly, that patient did not show shortness of stature, and that could be due to the haploinsufficiency of other genes localized in the flanking regions. Contribution of GH alterations and possible GH therapy should be further considered in WHS patients. Copyright 2004 Wiley-Liss, Inc.

Concurrent Medical Conditions and Health Care Use and Needs among Children with Learning and Behavioral Developmental Disabilities, National Health Interview Survey, 2006-2010

ERIC Educational Resources Information Center

Schieve, Laura A.; Gonzalez, Vanessa; Boulet, Sheree L.; Visser, Susanna N.; Rice, Catherine E.; Braun, Kim Van Naarden; Boyle, Coleen A.

2012-01-01

Studies document various associated health risks for children with developmental disabilities (DDs). Further study is needed by disability type. Using the 2006-2010 National Health Interview Surveys, we assessed the prevalence of numerous medical conditions (e.g. asthma, frequent diarrhea/colitis, seizures), health care use measures (e.g. seeing a…

Non-parametric early seizure detection in an animal model of temporal lobe epilepsy

NASA Astrophysics Data System (ADS)

Talathi, Sachin S.; Hwang, Dong-Uk; Spano, Mark L.; Simonotto, Jennifer; Furman, Michael D.; Myers, Stephen M.; Winters, Jason T.; Ditto, William L.; Carney, Paul R.

2008-03-01

The performance of five non-parametric, univariate seizure detection schemes (embedding delay, Hurst scale, wavelet scale, nonlinear autocorrelation and variance energy) were evaluated as a function of the sampling rate of EEG recordings, the electrode types used for EEG acquisition, and the spatial location of the EEG electrodes in order to determine the applicability of the measures in real-time closed-loop seizure intervention. The criteria chosen for evaluating the performance were high statistical robustness (as determined through the sensitivity and the specificity of a given measure in detecting a seizure) and the lag in seizure detection with respect to the seizure onset time (as determined by visual inspection of the EEG signal by a trained epileptologist). An optimality index was designed to evaluate the overall performance of each measure. For the EEG data recorded with microwire electrode array at a sampling rate of 12 kHz, the wavelet scale measure exhibited better overall performance in terms of its ability to detect a seizure with high optimality index value and high statistics in terms of sensitivity and specificity.

Maternal Obesity: Risks for Developmental Delays in Early Childhood.

PubMed

Duffany, Kathleen O'Connor; McVeigh, Katharine H; Kershaw, Trace S; Lipkind, Heather S; Ickovics, Jeannette R

2016-02-01

To assess the risk for neurodevelopmental delays for children of mothers who were obese (≥200 pounds) prior to pregnancy, and to characterize delays associated with maternal obesity among children referred to and found eligible to receive Early Intervention Program services. We conducted a retrospective cohort study (N = 541,816) using a population-based New York City data warehouse with linked birth and Early Intervention data. Risks for children suspected of a delay and 'significantly delayed', with two moderate or one severe delay, were calculated. Among the group of children eligible by delay for Early Intervention, analyses assessed risk for being identified with a moderate-to-severe delay across each of five functional domains as well as risks for multiple delays. Children of mothers who were obese were more likely to be suspected of a delay (adjusted RR 1.19 [CI 1.15-1.22]) and borderline association for 'significantly delayed' (adjusted RR 1.01 [CI 1.00-1.02). Among children eligible by delay, children of mothers who were obese evidenced an increased risk for moderate-to-severe cognitive (adjusted RR 1.04 [CI 1.02-1.07]) and physical (adjusted RR 1.04 [CI 1.01-1.08]) delays and for global developmental delay (adjusted RR 1.05 [CI 1.01-1.08]). Maternal obesity is associated with increased risk of developmental delay in offspring. Among children with moderate or severe delays, maternal obesity is associated with increased risk of cognitive and physical delays as well as with increased risk for global developmental delay. While causation remains uncertain, this adds to the growing body of research reporting an association between maternal obesity and neurodevelopmental delays in offspring.

Seizures and pain uncertainty associated with parenting stress and Rett syndrome.

PubMed

Byiers, Breanne J; Tervo, Raymond C; Feyma, Timothy J; Symons, Frank J

2014-04-01

Data were collected parenting stress, adaptive behavior, pain, and health issues from the caregivers of 35 girls and women with Rett syndrome (mean age = 20.3). A majority (60%) of parents reported stress in the clinical range on at least 1 subscale of the Parenting Stress Index-Short Form. Seizures and uncertainty about their daughter's gastrointestinal pain experience were significantly associated with higher levels of parenting stress. No other child factors (adaptive behavior, age, residential status) were significantly related to parenting stress. Factors related to chronic health concerns (seizures, ambiguous pain presentation) may be important when considering family stress issues in relation to general outcomes for girls with Rett syndrome and related developmental disorders.

Chromosomal Microarray With Clinical Diagnostic Utility in Children With Developmental Delay or Intellectual Disability.

PubMed

Lee, Jin Sook; Hwang, Hee; Kim, Soo Yeon; Kim, Ki Joong; Choi, Jin Sun; Woo, Mi Jung; Choi, Young Min; Jun, Jong Kwan; Lim, Byung Chan; Chae, Jong Hee

2018-09-01

Chromosomal microarray (CMA) testing is a first-tier test for patients with developmental delay, autism, or congenital anomalies. It increases diagnostic yield for patients with developmental delay or intellectual disability. In some countries, including Korea, CMA testing is not yet implemented in clinical practice. We assessed the diagnostic utility of CMA testing in a large cohort of patients with developmental delay or intellectual disability in Korea. We conducted a genome-wide microarray analysis of 649 consecutive patients with developmental delay or intellectual disability at the Seoul National University Children's Hospital. Medical records were reviewed retrospectively. Pathogenicity of detected copy number variations (CNVs) was evaluated by referencing previous reports or parental testing using FISH or quantitative PCR. We found 110 patients to have pathogenic CNVs, which included 100 deletions and 31 duplications of 270 kb to 30 Mb. The diagnostic yield was 16.9%, demonstrating the diagnostic utility of CMA testing in clinic. Parental testing was performed in 66 patients, 86.4% of which carried de novo CNVs. In eight patients, pathogenic CNVs were inherited from healthy parents with a balanced translocation, and genetic counseling was provided to these families. We verified five rarely reported deletions on 2p21p16.3, 3p21.31, 10p11.22, 14q24.2, and 21q22.13. This study demonstrated the clinical utility of CMA testing in the genetic diagnosis of patients with developmental delay or intellectual disability. CMA testing should be included as a clinical diagnostic test for all children with developmental delay or intellectual disability. © The Korean Society for Laboratory Medicine.

The Usefulness of M-B CDI-K Short Form as Screening Test in Children With Language Developmental Delay.

PubMed

Kim, Seong Woo; Jeon, Ha Ra; Park, Eun Ji; Kim, Hyo In; Jung, Da Wa; Woo, Mee Ryung

2014-06-01

To investigate the usefulness of MacArthur-Bates Communicative Development Inventories-Korean (M-B CDI-K) short form as a screening test in children with language developmental delay. From April 2010 to May 2012, a total of 87 patients visited the department of physical medicine and rehabilitation of National Health Insurance Service Ilsan Hospital with the complaint of language developmental delay and were enrolled in this study. All patients took M-B CDI-K short form and Sequenced Language Scale for Infants (SELSI) or Preschool Receptive-Expressive Language Scale (PRES) according to their age. The study group consisted of 58 male patients and 29 female patients and the mean age was 25.9 months. The diagnosis are global developmental delay in 26 patients, selective language impairment in 31 patients, articulation disorder in 7 patients, cerebral palsy in 8 patients, autism spectrum disorder in 4 patients, motor developmental delay in 4 patients, and others in 7 patients. Seventy-one patients are diagnosed with language developmental delay in SELSI or PRES and of them showed 69 patients a high risk in the M-B CDI-K short form. Sixteen patients are normal in SELSI or PRES and of them showed 14 patients non-high risk in the M-B CDI-K short form. The M-B CDI-K short form has 97.2% sensitivity, 87.5% specificity, a positive predictive value of 0.97, and a negative predictive value of 0.88. The M-B CDI-K short form has a high sensitivity and specificity so it is considered as an useful screening tool in children with language developmental delay. Additional researches targeting normal children will be continued to supply the specificity of the M-B CDI-K short form.

High prevalence of developmental delay among children under three years of age in poverty-stricken areas of China.

PubMed

Wei, Q W; Zhang, J X; Scherpbier, R W; Zhao, C X; Luo, S S; Wang, X L; Guo, S F

2015-12-01

Poverty and its associated factors put children at risk for developmental delay. The aim of this study was to describe the neurodevelopment of children under three years of age in poverty-stricken areas of China and explore possible associated factors. A cross-sectional survey was conducted among 2837 children aged 1-35 months in poverty-stricken areas of China. Characteristics of the child, caregiver, and family were collected through face-to-face caregiver interviews. Developmental delay was explored with the five-domain, structured, parent-completed Ages and Stages Questionnaire. The Zung Self-rating Depression Scale was used to assess depressive symptoms of the caregivers. The Chi-squared test and multivariate logistic regression analyses were used to explore associated factors. Of the children, 39.7% (95% confidence interval, 37.9-41.5) had developmental delay in at least one of the five domains. For the domains of communication, gross motor, fine motor, problem solving, and personal-social skills, the prevalence was 11.5%, 18.5%, 21.4%, 18.4%, and 17.9%, respectively. Significant predictors of increased odds of developmental delay included the child having no toys (odds ratio [OR] = 2.31), the caregiver having depression (OR = 2.24), insufficient learning activities (OR = 1.65), and more children in the family (OR = 1.16). The high prevalence of developmental delay in children younger than three years in poverty-stricken areas of China and the presence of risk factors for developmental delay such as inadequate learning resources and activities in the home, caregiver depression, and low family income highlight the need for early identification and interventions. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Parenting Stress and Depression in Children with Mental Retardation and Developmental Disabilities.

ERIC Educational Resources Information Center

Kobe, Frank H.

1994-01-01

This study of 29 children with developmental delays found that parent ratings of children's depression were significantly associated with maternal depression, negative self-image, anxiety, and conduct problems. Data suggest that children with developmental delays exhibit a similar pattern of symptoms and associated characteristics to those found…

Patient-Specific Early Seizure Detection from Scalp EEG

PubMed Central

Minasyan, Georgiy R.; Chatten, John B.; Chatten, Martha Jane; Harner, Richard N.

2010-01-01

Objective Develop a method for automatic detection of seizures prior to or immediately after clinical onset using features derived from scalp EEG. Methods This detection method is patient-specific. It uses recurrent neural networks and a variety of input features. For each patient we trained and optimized the detection algorithm for two cases: 1) during the period immediately preceding seizure onset, and 2) during the period immediately following seizure onset. Continuous scalp EEG recordings (duration 15 – 62 h, median 25 h) from 25 patients, including a total of 86 seizures, were used in this study. Results Pre-onset detection was successful in 14 of the 25 patients. For these 14 patients, all of the testing seizures were detected prior to seizure onset with a median pre-onset time of 51 sec and false positive rate was 0.06/h. Post-onset detection had 100% sensitivity, 0.023/hr false positive rate and median delay of 4 sec after onset. Conclusions The unique results of this study relate to pre-onset detection. Significance Our results suggest that reliable pre-onset seizure detection may be achievable for a significant subset of epilepsy patients without use of invasive electrodes. PMID:20461014

Genetics Home Reference: Partington syndrome

MedlinePlus

... of autism spectrum disorders that affect communication and social interaction. Recurrent seizures (epilepsy) may also occur in Partington ... Kennedy Shriver National Institute of Child Health and Human Development: Intellectual and Developmental Disabilities National Institute of ...

Collagen matrix as an inlay in endoscopic skull base reconstruction.

PubMed

Oakley, G M; Christensen, J M; Winder, M; Jonker, B P; Davidson, A; Steel, T; Teo, C; Harvey, R J

2018-03-01

Multi-layer reconstruction has become standard in endoscopic skull base surgery. The inlay component used can vary among autografts, allografts, xenografts and synthetics, primarily based on surgeon preference. The short- and long-term outcomes of collagen matrix in skull base reconstruction are described. A case series of patients who underwent endoscopic skull base reconstruction with collagen matrix inlay were assessed. Immediate peri-operative outcomes (cerebrospinal fluid leak, meningitis, ventriculitis, intracranial bleeding, epistaxis, seizures) and delayed complications (delayed healing, meningoencephalocele, prolapse of reconstruction, delayed cerebrospinal fluid leak, ascending meningitis) were examined. Of 120 patients (51.0 ± 17.5 years, 41.7 per cent female), peri-operative complications totalled 12.7 per cent (cerebrospinal fluid leak, 3.3 per cent; meningitis, 3.3 per cent; other intracranial infections, 2.5 per cent; intracranial bleeding, 1.7 per cent; epistaxis, 1.7 per cent; and seizures, 0 per cent). Delayed complications did not occur in any patients. Collagen matrix is an effective inlay material. It provides robust long-term separation between sinus and cranial cavities, and avoids donor site morbidity, but carries additional cost.

Alexander Disease: A Novel Mutation in GFAP Leading to Epilepsia Partialis Continua.

PubMed

Bonthius, Daniel J; Karacay, Bahri

2016-06-01

Alexander disease is a genetically induced leukodystrophy, due to dominant mutations in the glial fibrillary acidic protein (GFAP ) gene, causing dysfunction of astrocytes. We have identified a novel GFAP mutation, associated with a novel phenotype for Alexander disease. A boy with global developmental delay and hypertonia was found to have a leukodystrophy. Genetic analysis revealed a heterozygous point mutation in exon 6 of the GFAP gene. The guanine-to-adenine change causes substitution of the normal glutamic acid codon (GAG) with a mutant lysine codon (AAG) at position 312 (E312 K mutation). At the age of 4 years, the child developed epilepsia partialis continua, consisting of unabating motor seizures involving the unilateral perioral muscles. Epilepsia partialis continua has not previously been reported in association with Alexander disease. Whether and how the E312 K mutation produces pathologic changes and clinical signs that are unique from other Alexander disease-inducing mutations in GFAP remain to be determined. © The Author(s) 2015.

A male case with CDKL5-associated encephalopathy manifesting transient methylmalonic acidemia.

PubMed

Akamine, Satoshi; Ishizaki, Yoshito; Sakai, Yasunari; Torisu, Hiroyuki; Fukai, Ryoko; Miyake, Noriko; Ohkubo, Kazuhiro; Koga, Hiroshi; Sanefuji, Masafumi; Sakata, Ayumi; Kimura, Masahiko; Yamaguchi, Seiji; Sakamoto, Osamu; Hara, Toshiro; Saitsu, Hirotomo; Matsumoto, Naomichi; Ohga, Shouichi

2018-03-03

Mutations in the X-linked gene CDKL5 cause early-onset epileptic encephalopathy and severe developmental delay. Because this disorder predominantly affects females, the full clinical spectrum of male patients remains elusive. We herein report a 16-year-old boy, who suffered from intractable seizures 20 days after birth. Serial electroencephalograms detected recurrent focal epileptiform discharges from age 4 months, which evolved to hypsarrhythmia later in infancy. Mass-spectrometric analyses revealed increase in urinary excretion of methylmalonic acid without perturbed concentrations of propionic acid, homocystein and methionine. Whole-exome sequencing identified a de novo, truncating mutation in CDKL5 (NM_003159.2:c.419dupA, p.Asn140Lysfs*8). Targeted sequencing excluded concomitant mutations in methylmalonic academia-associated genes. No methylmalonic acidemia has been reported in children with CDKL5 disorder. Extensive analyses on organic acid metabolism for males with CDKL5 mutations will gain more insight into their biochemical profiles in infancy. Copyright © 2018. Published by Elsevier Masson SAS.

A Novel Missense Mutation of Doublecortin: Mutation Analysis of Korean Patients with Subcortical Band Heterotopia

PubMed Central

Kim, Myeong-Kyu; Park, Man-Seok; Kim, Byeong-Chae; Cho, Ki-Hyun; Kim, Young-Seon; Kim, Jin-Hee; Heo, Tag; Kim, Eun-Young

2005-01-01

The neuronal migration disorders, X-linked lissencephaly syndrome (XLIS) and subcortical band heterotopia (SBH), also called "double cortex", have been linked to missense, nonsense, aberrant splicing, deletion, and insertion mutations in doublecortin (DCX) in families and sporadic cases. Most DCX mutations identified to date are located in two evolutionarily conserved domains. We performed mutation analysis of DCX in two Korean patients with SBH. The SBH patients had mild to moderate developmental delays, drug-resistant generalized seizures, and diffuse thick SBH upon brain MRI. Sequence analysis of the DCX coding region in Patient 1 revealed a c.386 C>T change in exon 3. The sequence variation results in a serine to leucine amino acid change at position 129 (S129L), which has not been found in other family members of Patient 1 or in a large panel of 120 control X-chromosomes. We report here a novel c.386 C>T mutation of DCX that is responsible for SBH. PMID:16100463

Inborn Errors of Metabolism and Epilepsy: Current Understanding, Diagnosis, and Treatment Approaches

PubMed Central

Sharma, Suvasini; Prasad, Asuri N.

2017-01-01

Inborn errors of metabolism (IEM) are a rare cause of epilepsy, but seizures and epilepsy are frequently encountered in patients with IEM. Since these disorders are related to inherited enzyme deficiencies with resulting effects on metabolic/biochemical pathways, the term “metabolic epilepsy” can be used to include these conditions. These epilepsies can present across the life span, and share features of refractoriness to anti-epileptic drugs, and are often associated with co-morbid developmental delay/regression, intellectual, and behavioral impairments. Some of these disorders are amenable to specific treatment interventions; hence timely and appropriate diagnosis is critical to improve outcomes. In this review, we discuss those disorders in which epilepsy is a dominant feature and present an approach to the clinical recognition, diagnosis, and management of these disorders, with a greater focus on primarily treatable conditions. Finally, we propose a tiered approach that will permit a clinician to systematically investigate, identify, and treat these rare disorders. PMID:28671587

Exposure of children with developmental delay to social determinants of poor health: cross-sectional case record review study.

PubMed

Emerson, E; Brigham, P

2015-03-01

Research on child development in general has highlighted the importance that the family environment plays in mediating the pathway between exposure to low socio-economic position (SEP) and child well-being. While child developmental models in intellectual disability have highlighted the interplay between social context, family environment and child development, little empirical work has attempted to formally evaluate the evidence in support of specific mediating pathways between low SEP and child outcomes. Secondary analysis of cross-sectional confidentialized needs analysis data collected in three Primary Care Trusts in England covering a total population of 1.25 million people. Case record reviews were undertaken for 46 023 households, 2236 (4.9%) of which contained a child in the target age range with developmental delay. Children with developmental delay, when compared with their non-disabled peers, were at significantly increased risk of poorer health outcomes and of being exposed to a wide range of social determinants of poor health. Controlling for between-group differences in exposure to social determinants of poor health reduced the risk of developmental delay being associated with poorer health outcomes by 45% for behaviour problems and 89% for risk of significant harm. For children with developmental delay, parenting difficulties appears to play a particularly significant role in partially mediating the effects of low SEP. The findings of the present study point to the potential effectiveness of family-focused early intervention to prevent the emergence and escalation of behavioural difficulties and health problems in children with developmental delay. © 2014 John Wiley & Sons Ltd.

Trajectories of Developmental Functioning among Children of Adolescent Mothers: Factors Associated with Risk for Delay

ERIC Educational Resources Information Center

Jahromi, Laudan B.; Umaña-Taylor, Adriana J.; Updegraff, Kimberly A.; Zeiders, Katharine H.

2016-01-01

Children of adolescent mothers are at risk for developmental delays. Less is known about the heterogeneity in these children's developmental trajectories, and factors associated with different patterns of development. This longitudinal study used latent class growth analysis (LCGA) to identify distinct trajectories in children of Mexican-origin…

Myristicin and phenytoin toxicity in an infant

PubMed Central

Sivathanu, Shobhana; Sampath, Sowmya; David, Henry Suresh; Rajavelu, Kulandai Kasthuri

2014-01-01

A developmentally normal infant presented with repeated episodes of afebrile status epilepticus following nutmeg ingestion. He had developed two episodes of afebrile status epilepticus and had received different treatments earlier, but the details of treatment were not available. On admission, he redeveloped convulsions and loading doses of phenytoin, phenobarbitone and midazolam were administered. However, seizures persisted and extrapyramidal movements, nystagmus and visual dysfunction were noted. Iatrogenic phenytoin toxicity was considered and confirmed by drug levels. His symptoms completely disappeared after discontinuation of phenytoin therapy. The initial seizures were attributed to myristicin, an active component of nutmeg, because of the temporal association. However, the subsequent seizures were due to phenytoin toxicity caused by administration of multiple loading doses. This case highlights that nutmeg, a spice, can cause serious toxic effects like status epilepticus. Furthermore, treatment of status epilepticus with phenytoin can cause iatrogenic seizures due to its narrow therapeutic range. PMID:24903724

Environmental Enrichment Decreases Asphyxia-Induced Neurobehavioral Developmental Delay in Neonatal Rats

PubMed Central

Kiss, Peter; Vadasz, Gyongyver; Kiss-Illes, Blanka; Horvath, Gabor; Tamas, Andrea; Reglodi, Dora; Koppan, Miklos

2013-01-01

Perinatal asphyxia during delivery produces long-term disability and represents a major problem in neonatal and pediatric care. Numerous neuroprotective approaches have been described to decrease the effects of perinatal asphyxia. Enriched environment is a popular strategy to counteract nervous system injuries. The aim of the present study was to investigate whether enriched environment is able to decrease the asphyxia-induced neurobehavioral developmental delay in neonatal rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by caesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily and motor coordination weekly. Our results show that rats undergoing perinatal asphyxia had a marked developmental delay and worse performance in motor coordination tests. However, pups kept in enriched environment showed a decrease in the developmental delay observed in control asphyctic pups. Rats growing up in enriched environment did not show decrease in weight gain after the first week and the delay in reflex appearance was not as marked as in control rats. In addition, the development of motor coordination was not as strikingly delayed as in the control group. Short-term neurofunctional outcome are known to correlate with long-term deficits. Our results thus show that enriched environment could be a powerful strategy to decrease the deleterious developmental effects of perinatal asphyxia. PMID:24232451

Environmental enrichment decreases asphyxia-induced neurobehavioral developmental delay in neonatal rats.

PubMed

Kiss, Peter; Vadasz, Gyongyver; Kiss-Illes, Blanka; Horvath, Gabor; Tamas, Andrea; Reglodi, Dora; Koppan, Miklos

2013-11-13

Perinatal asphyxia during delivery produces long-term disability and represents a major problem in neonatal and pediatric care. Numerous neuroprotective approaches have been described to decrease the effects of perinatal asphyxia. Enriched environment is a popular strategy to counteract nervous system injuries. The aim of the present study was to investigate whether enriched environment is able to decrease the asphyxia-induced neurobehavioral developmental delay in neonatal rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by caesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily and motor coordination weekly. Our results show that rats undergoing perinatal asphyxia had a marked developmental delay and worse performance in motor coordination tests. However, pups kept in enriched environment showed a decrease in the developmental delay observed in control asphyctic pups. Rats growing up in enriched environment did not show decrease in weight gain after the first week and the delay in reflex appearance was not as marked as in control rats. In addition, the development of motor coordination was not as strikingly delayed as in the control group. Short-term neurofunctional outcome are known to correlate with long-term deficits. Our results thus show that enriched environment could be a powerful strategy to decrease the deleterious developmental effects of perinatal asphyxia.

Adaptive developmental delay in Chagas disease vectors: an evolutionary ecology approach.

PubMed

Menu, Frédéric; Ginoux, Marine; Rajon, Etienne; Lazzari, Claudio R; Rabinovich, Jorge E

2010-05-25

The developmental time of vector insects is important in population dynamics, evolutionary biology, epidemiology and in their responses to global climatic change. In the triatomines (Triatominae, Reduviidae), vectors of Chagas disease, evolutionary ecology concepts, which may allow for a better understanding of their biology, have not been applied. Despite delay in the molting in some individuals observed in triatomines, no effort was made to explain this variability. We applied four methods: (1) an e-mail survey sent to 30 researchers with experience in triatomines, (2) a statistical description of the developmental time of eleven triatomine species, (3) a relationship between development time pattern and climatic inter-annual variability, (4) a mathematical optimization model of evolution of developmental delay (diapause). 85.6% of responses informed on prolonged developmental times in 5(th) instar nymphs, with 20 species identified with remarkable developmental delays. The developmental time analysis showed some degree of bi-modal pattern of the development time of the 5(th) instars in nine out of eleven species but no trend between development time pattern and climatic inter-annual variability was observed. Our optimization model predicts that the developmental delays could be due to an adaptive risk-spreading diapause strategy, only if survival throughout the diapause period and the probability of random occurrence of "bad" environmental conditions are sufficiently high. Developmental delay may not be a simple non-adaptive phenotypic plasticity in development time, and could be a form of adaptive diapause associated to a physiological mechanism related to the postponement of the initiation of reproduction, as an adaptation to environmental stochasticity through a spreading of risk (bet-hedging) strategy. We identify a series of parameters that can be measured in the field and laboratory to test this hypothesis. The importance of these findings is discussed in terms of global climatic change and epidemiological consequences.

Age- and sex-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters

PubMed Central

Kang, Seok Kyu; Markowitz, Geoffrey J.; Kim, Shin Tae; Johnston, Michael V.; Kadam, Shilpa D.

2015-01-01

Ischemia in the immature brain is an important cause of neonatal seizures. Temporal evolution of acquired neonatal seizures and their response to anticonvulsants are of great interest, given the unreliability of the clinical correlates and poor efficacy of first-line anti-seizure drugs. The expression and function of the electroneutral chloride co-transporters KCC2 and NKCC1 influence the anti-seizure efficacy of GABAA-agonists. To investigate ischemia-induced seizure susceptibility and efficacy of the GABAA-agonist phenobarbital (PB), with NKCC1 antagonist bumetanide (BTN) as an adjunct treatment, we utilized permanent unilateral carotid-ligation to produce acute ischemic-seizures in post-natal day 7, 10, and 12 CD1 mice. Immediate post-ligation video-electroencephalograms (EEGs) quantitatively evaluated baseline and post-treatment seizure burdens. Brains were examined for stroke-injury and western blot analyses to evaluate the expression of KCC2 and NKCC1. Severity of acute ischemic seizures post-ligation was highest at P7. PB was an efficacious anti-seizure agent at P10 and P12, but not at P7. BTN failed as an adjunct, at all ages tested and significantly blunted PB-efficacy at P10. Significant acute post-ischemic downregulation of KCC2 was detected at all ages. At P7, males displayed higher age-dependent seizure susceptibility, associated with a significant developmental lag in their KCC2 expression. This study established a novel neonatal mouse model of PB-resistant seizures that demonstrates age/sex-dependent susceptibility. The age-dependent profile of KCC2 expression and its post-insult downregulation may underlie the PB-resistance reported in this model. Blocking NKCC1 with low-dose BTN following PB treatment failed to improve PB-efficacy. PMID:26029047

Age- and sex-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters.

PubMed

Kang, Seok Kyu; Markowitz, Geoffrey J; Kim, Shin Tae; Johnston, Michael V; Kadam, Shilpa D

2015-01-01

Ischemia in the immature brain is an important cause of neonatal seizures. Temporal evolution of acquired neonatal seizures and their response to anticonvulsants are of great interest, given the unreliability of the clinical correlates and poor efficacy of first-line anti-seizure drugs. The expression and function of the electroneutral chloride co-transporters KCC2 and NKCC1 influence the anti-seizure efficacy of GABAA-agonists. To investigate ischemia-induced seizure susceptibility and efficacy of the GABAA-agonist phenobarbital (PB), with NKCC1 antagonist bumetanide (BTN) as an adjunct treatment, we utilized permanent unilateral carotid-ligation to produce acute ischemic-seizures in post-natal day 7, 10, and 12 CD1 mice. Immediate post-ligation video-electroencephalograms (EEGs) quantitatively evaluated baseline and post-treatment seizure burdens. Brains were examined for stroke-injury and western blot analyses to evaluate the expression of KCC2 and NKCC1. Severity of acute ischemic seizures post-ligation was highest at P7. PB was an efficacious anti-seizure agent at P10 and P12, but not at P7. BTN failed as an adjunct, at all ages tested and significantly blunted PB-efficacy at P10. Significant acute post-ischemic downregulation of KCC2 was detected at all ages. At P7, males displayed higher age-dependent seizure susceptibility, associated with a significant developmental lag in their KCC2 expression. This study established a novel neonatal mouse model of PB-resistant seizures that demonstrates age/sex-dependent susceptibility. The age-dependent profile of KCC2 expression and its post-insult downregulation may underlie the PB-resistance reported in this model. Blocking NKCC1 with low-dose BTN following PB treatment failed to improve PB-efficacy.

Septo-Optic Dysplasia

MedlinePlus

... children with SOD have normal intelligence, others have learning disabilities. Most, however, are developmentally delayed due to vision ... children with SOD have normal intelligence, others have learning disabilities. Most, however, are developmentally delayed due to vision ...

Discrimination Acquisition in Children with Developmental Disabilities under Immediate and Delayed Reinforcement

ERIC Educational Resources Information Center

Sy, Jolene R.; Vollmer, Timothy R.

2012-01-01

We evaluated the discrimination acquisition of individuals with developmental disabilities under immediate and delayed reinforcement. In Experiment 1, discrimination between two alternatives was examined when reinforcement was immediate or delayed by 20 s, 30 s, or 40 s. In Experiment 2, discrimination between 2 alternatives was compared across an…

Promoting Healthy Weight among Children with Developmental Delays

ERIC Educational Resources Information Center

Natale, Ruby R.; Camejo, Stephanie T.; Asfour, Lila; Uhlhorn, Susan B.; Delamater, Alan; Messiah, Sarah E.

2017-01-01

An extensive body of research demonstrates a higher prevalence of obesity among children with developmental delays (DD) versus children without delays. This analysis examined the effectiveness of a randomized controlled trial to promote healthy weight in a subsample of preschool-age children with DD (n = 71) on the adoption of quality nutrition…

Protective effects of S+ ketamine and atropine against lethality and brain damage during soman-induced status epilepticus in guinea-pigs.

PubMed

Dorandeu, Frederic; Baille, Valerie; Mikler, John; Testylier, Guy; Lallement, Guy; Sawyer, Thomas; Carpentier, Pierre

2007-05-20

Soman poisoning is known to induce full-blown tonic-clonic seizures, status epilepticus (SE), seizure-related brain damage (SRBD) and lethality. Previous studies in guinea-pigs have shown that racemic ketamine (KET), with atropine sulfate (AS), is very effective in preventing death, stopping seizures and protecting sensitive brain areas when given up to 1h after a supra-lethal challenge of soman. The active ketamine isomer, S(+) ketamine (S-KET), is more potent than the racemic mixture and it also induces less side-effects. To confirm the efficacy of KET and to evaluate the potential of S-KET for delayed medical treatment of soman-induced SE, we studied different S-KET dose regimens using the same paradigm used with KET. Guinea-pigs received pyridostigmine (26 microg/kg, IM) 30min before soman (62 microg/kg, 2 LD(50), IM), followed by therapy consisting of atropine methyl nitrate (AMN) (4 mg/kg, IM) 1min following soman exposure. S-KET, with AS (10mg/kg), was then administered IM at different times after the onset of seizures, starting at 1h post-soman exposure. The protective efficacy of S-KET proved to be comparable to KET against lethality and SRBD, but at doses two to three times lower. As with KET, delaying treatment by 2h post-poisoning greatly reduced efficacy. Conditions that may have led to an increased S-KET brain concentration (increased doses or number of injections, adjunct treatment with the oxime HI-6) did not prove to be beneficial. In summary, these observations confirm that ketamine, either racemic or S-KET, in association with AS and possibly other drugs, could be highly effective in the delayed treatment of severe soman intoxication.

Antisense reduction of tau in adult mice protects against seizures.

PubMed

DeVos, Sarah L; Goncharoff, Dustin K; Chen, Guo; Kebodeaux, Carey S; Yamada, Kaoru; Stewart, Floy R; Schuler, Dorothy R; Maloney, Susan E; Wozniak, David F; Rigo, Frank; Bennett, C Frank; Cirrito, John R; Holtzman, David M; Miller, Timothy M

2013-07-31

Tau, a microtubule-associated protein, is implicated in the pathogenesis of Alzheimer's Disease (AD) in regard to both neurofibrillary tangle formation and neuronal network hyperexcitability. The genetic ablation of tau substantially reduces hyperexcitability in AD mouse lines, induced seizure models, and genetic in vivo models of epilepsy. These data demonstrate that tau is an important regulator of network excitability. However, developmental compensation in the genetic tau knock-out line may account for the protective effect against seizures. To test the efficacy of a tau reducing therapy for disorders with a detrimental hyperexcitability profile in adult animals, we identified antisense oligonucleotides that selectively decrease endogenous tau expression throughout the entire mouse CNS--brain and spinal cord tissue, interstitial fluid, and CSF--while having no effect on baseline motor or cognitive behavior. In two chemically induced seizure models, mice with reduced tau protein had less severe seizures than control mice. Total tau protein levels and seizure severity were highly correlated, such that those mice with the most severe seizures also had the highest levels of tau. Our results demonstrate that endogenous tau is integral for regulating neuronal hyperexcitability in adult animals and suggest that an antisense oligonucleotide reduction of tau could benefit those with epilepsy and perhaps other disorders associated with tau-mediated neuronal hyperexcitability.

DNA Damage Analysis in Children with Non-syndromic Developmental Delay by Comet Assay.

PubMed

Susai, Surraj; Chand, Parkash; Ballambattu, Vishnu Bhat; Hanumanthappa, Nandeesha; Veeramani, Raveendranath

2016-05-01

Majority of the developmental delays in children are non-syndromic and they are believed to have an underlying DNA damage, though not well substantiated. Hence the present study was carried out to find out if there is any increased DNA damage in children with non-syndromic developmental delay by using the comet assay. The present case-control study was undertaken to assess the level of DNA damage in children with non syndromic developmental delay and compare the same with that of age and sex matched controls using submarine gel electrophoresis (Comet Assay). The blood from clinically diagnosed children with non syndromic developmental delay and controls were subjected for alkaline version of comet assay - Single cell gel electrophoresis using lymphocytes isolated from the peripheral blood. The comets were observed under a bright field microscope; photocaptured and scored using the Image J image quantification software. Comet parameters were compared between the cases and controls and statistical analysis and interpretation of results was done using the statistical software SPSS version 20. The mean comet tail length in cases and control was 20.77+7.659μm and 08.97+4.398μm respectively which was statistically significant (p<0.001). Other comet parameters like total comet length and % DNA in tail also showed a statistically significant difference (p < 0.001) between cases and controls. The current investigation unraveled increased levels of DNA damage in children with non syndromic developmental delay when compared to the controls.

Nonconvulsive electrographic seizures after traumatic brain injury result in a delayed, prolonged increase in intracranial pressure and metabolic crisis.

PubMed

Vespa, Paul M; Miller, Chad; McArthur, David; Eliseo, Mathew; Etchepare, Maria; Hirt, Daniel; Glenn, Thomas C; Martin, Neil; Hovda, David

2007-12-01

To determine whether nonconvulsive electrographic post-traumatic seizures result in increases in intracranial pressure and microdialysis lactate/pyruvate ratio. Prospective monitoring with retrospective data analysis. Single center academic neurologic intensive care unit. Twenty moderate to severe traumatic brain injury patients (Glasgow Coma Score 3-13). Continuous electroencephalography and cerebral microdialysis were performed for 7 days after injury. Ten patients had seizures and were compared with a matched cohort of traumatic brain injury patients without seizures. The seizures were repetitive and constituted status epilepticus in seven of ten patients. Using a within-subject design, post-traumatic seizures resulted in episodic increases in intracranial pressure (22.4 +/- 7 vs. 12.8 +/- 4.3 mm Hg; p < .001) and an episodic increase in lactate/pyruvate ratio (49.4 +/- 16 vs. 23.8 +/- 7.6; p < .001) in the seizure group. Using a between-subjects comparison, the seizure group demonstrated a higher mean intracranial pressure (17.6 +/- 6.5 vs. 12.2 +/- 4.2 mm Hg; p < .001), a higher mean lactate/pyruvate ratio (38.6 +/- 18 vs. 27 +/- 9; p < .001) compared with nonseizure patients. The intracranial pressure and lactate/pyruvate ratio remained elevated beyond postinjury hour 100 in the seizure group but not the nonseizure group (p < .02). Post-traumatic seizures result in episodic as well as long-lasting increases in intracranial pressure and microdialysis lactate/pyruvate ratio. These data suggest that post-traumatic seizures represent a therapeutic target for patients with traumatic brain injury.

Hypoparathyroidism-retardation-dysmorphism syndrome in a girl: A new variant not caused by a TBCE mutation--clinical report and review.

PubMed

Courtens, Winnie; Wuyts, Wim; Poot, Martin; Szuhai, Karoly; Wauters, Jan; Reyniers, Edwin; Eleveld, Marc; Diaz, George; Nöthen, Markus M; Parvari, Ruti

2006-03-15

Hypoparathyroidism-retardation-dysmorphism (HRD) or Sanjad-Sakati syndrome (SSS) (OMIM 241410) is a rare autosomal recessive (AR) inherited condition, characterized by congenital hypoparathyroidism (hypoPTH), retardation, seizures, and a typical facial dysmorphism, consisting of prominent forehead, deep-set eyes, and abnormal external ears. This disorder has been mapped to the long arm of chromosome 1 (1q42-q43) and mutations in the gene coding for tubulin-specific chaperone E (TBCE) have been identified as the cause of the disease. Mutations in the same gene were also reported in patients with AR Kenny-Caffey syndrome (KCS). We report on a 41/2-year-old girl with congenital hypoPTH, seizures, developmental delay, and a facial dysmorphism, compatible with HRD syndrome. Mutation analyses revealed no mutations in the TBCE gene. In addition, normal TBCE protein and alpha-tubulin immunostaining were observed in a lymphoblastoid line derived from the patient, excluding the TBCE gene as the causative gene of the syndrome in this patient. A de novo microduplication of probe RP11-262I1 on 4q35 in the proposita was detected by microarray analyses, but this could not be confirmed by additional studies. We review and discuss the clinical findings of our case and those of the other reported cases with SSS and AR KCS. We conclude that a second gene locus for this disorder seems probable and that 4q35 needs further evaluation as a candidate region.

Long-lasting Effects of Minocycline on Behavior in Young but not Adult Fragile X Mice

PubMed Central

Dansie, Lorraine E.; Phommahaxay, Kelly; Okusanya, Ayodeji G.; Uwadia, Jessica; Huang, Mike; Rotschafer, Sarah E.; Razak, Khaleel A.; Ethell, Douglas W.; Ethell, Iryna M.

2013-01-01

Fragile X Syndrome (FXS) is the most common single-gene inherited form of intellectual disability with behaviors characteristic of autism. People with FXS display childhood seizures, hyperactivity, anxiety, developmental delay, attention deficits, and visual-spatial memory impairment, as well as a propensity for obsessive-compulsive disorder (OCD). Several of these aberrant behaviors and FXS-associated synaptic irregularities also occur in “fragile X mental retardation gene” knock-out (Fmr1 KO) mice. We previously reported that minocycline promotes the maturation of dendritic spines - postsynaptic sites for excitatory synapses - in the developing hippocampus of Fmr1 KO mice, which may underlie the beneficial effects of minocycline on anxiolytic behavior in young Fmr1 KO mice. In this study, we compared the effectiveness of minocycline treatment in young and adult Fmr1 KO mice, and determined the dependence of behavioral improvements on short-term versus long-term minocycline administration. We found that 4 and 8 week long treatments significantly reduced locomotor activity in both young and adult Fmr1 KO mice. Some behavioral improvements persisted in young mice post-treatment, but in adults the beneficial effects were lost soon after minocycline treatment was stopped. We also show, for the first time, that minocycline treatment partially attenuates the number and severity of audiogenic seizures in Fmr1 KO mice. This report provides further evidence that minocycline treatment has immediate and long-lasting benefits on FXS-associated behaviors in the Fmr1 KO mouse model. PMID:23660195

The expanding clinical phenotype of the tRNA{sup Leu(UUR)} A{r_arrow}G mutation at np 3243 of mitochondrial DNA: Diabetic embryopathy associated with mitochondrial cytopathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feigenbaum, A.; Chitayat, D.; Robinson, B.

1996-04-24

We describe a family which demonstrates and expands the extreme clinical variability now known to be associated with the A{r_arrow}G transition at nucleotide position 3243 of the mitochondrial DNA. The propositus presented at birth with clinical manifestations consistent with diabetic embryopathy including anal atresia, caudal dysgenesis, and multicystic dysplastic kidneys. His co-twin was normal at birth, but at 3 months of life, presented with intractable seizures later associated with developmental delay. The twins` mother developed diabetes mellitus type I at the age of 20 years and gastrointestinal problems at 22 years. Since age 19 years, the maternal aunt has hadmore » recurrent strokes, seizures, mental deterioration and deafness, later diagnosed as MELAS syndrome due to the tRNA{sup Leu(UUR)} A{r_arrow}G mutation. A maternal uncle had diabetes mellitus type I, deafness, and normal intellect, and died at 35 years after recurrent strokes. This pedigree expands the known clinical phenotype associated with tRNA{sup Leu(UUR)} A{r_arrow}G mutation and raises the possibility that, in some cases, diabetic embryopathy may be due to a mitochondrial cytopathy that affects both the mother`s pancreas (and results in diabetes mellitus and the metabolic dysfunction associated with it) and the embryonic/fetal and placental tissues which make the embryo more vulnerable to this insult. 33 refs., 1 tab.« less

The Efficacy of Arabic Version of the Developmental Assessment of Young Children Second Edition (DAYC-2) Scale in Detecting Developmental Delay among Jordanian Children Aged Birth to 71 Months

ERIC Educational Resources Information Center

Saleh, Rawan M. Abu; Smadi, Jamil M.

2017-01-01

This study aimed to assess the efficacy of the developmental assessment of young children second edition (DAYC-2) Scale in detecting Developmental Delay among Jordanian children aged birth to 71 months. Firstly, the scale was translated and reviewed for language and cultural appropriateness. Secondly, the Arabic Jordanian version of the scale was…

The use of the Bayley Scales of Infant and Toddler Development III with clinical populations: a preliminary exploration.

PubMed

Milne, Susan; McDonald, Jenny; Comino, Elizabeth J

2012-02-01

In response to concerns that the Bayley Scales of Infant and Toddler Development III (BSIDIII) underestimate delay in clinical populations, this study explores developmental quotient scores as an alternative to composite scores for these children. One hundred and twenty-two children aged ≤42 months, referred for diagnosis of developmental disability from January 2007 to May 2010, were assessed, and their composite and developmental quotient scores on each scale were compared. Composite scores identified only 22% (cognitive), 27% (motor), and 47.5% (language) of children as having a developmental disability. Developmental quotient scores were significantly lower than composite scores, giving rates of developmental disability of 56.6% (cognitive), 48.4% (motor), and 74.6% (language) and more closely matching both clinical impressions of delay and the proportions of those children who were also delayed on standardized tests of adaptive function.

A Descriptive Study of Hyperlexia in a Clinically Referred Sample of Children with Developmental Delays.

ERIC Educational Resources Information Center

Grigorenok, Elena L.; Klin, Ami; Pauls, David L.; Senft, Riley; Hooper, Catalina; Volkmar, Fred

2002-01-01

This study of hyperlexia in 80 children with developmental delays found no significant differences in the frequency of hyperlexia in girls compared with boys; a significantly elevated frequency of hyperlexia in children diagnosed with pervasive developmental disorders (PDD) compared with children with non-PDD diagnoses; and a similar range of IQ…

Effects of Weighted Vests on the Engagement of Children with Developmental Delays and Autism

ERIC Educational Resources Information Center

Reichow, Brian; Barton, Erin E.; Sewell, Joanna Neely; Good, Leslie; Wolery, Mark

2010-01-01

The use of weighted vests for children with autism spectrum disorders and developmental disabilities is a common practice as part of sensory integration therapy programs. The purpose of the current investigation was to extend the research on the use of weighted vests for children with autism and developmental delays in a methodologically rigorous…

Hydrocephalus

MedlinePlus

... lethargy Nausea or vomiting Unstable balance Poor coordination Poor appetite Seizures Urinary incontinence Behavioral and cognitive changes Irritability Change in personality Decline in school performance Delays or problems with previously acquired skills, such ...

Sensitivity and specificity of memory and naming tests for identifying left temporal-lobe epilepsy.

PubMed

Umfleet, Laura Glass; Janecek, Julie K; Quasney, Erin; Sabsevitz, David S; Ryan, Joseph J; Binder, Jeffrey R; Swanson, Sara J

2015-01-01

The sensitivity and specificity of the Selective Reminding Test (SRT) Delayed Recall, Wechsler Memory Scale (WMS) Logical Memory, the Boston Naming Test (BNT), and two nonverbal memory measures for detecting lateralized dysfunction in association with side of seizure focus was examined in a sample of 143 patients with left or right temporal-lobe epilepsy (TLE). Scores on the SRT and BNT were statistically significantly lower in the left TLE group compared with the right TLE group, whereas no group differences emerged on the Logical Memory subtest. No significant group differences were found with nonverbal memory measures. When the SRT and BNT were both entered as predictors in a logistic regression, the BNT, although significant, added minimal value to the model beyond the variance accounted for by the SRT Delayed Recall. Both variables emerged as significant predictors of side of seizure focus when entered into separate regressions. Sensitivity and specificity of the SRT and BNT ranged from 56% to 65%. The WMS Logical Memory and nonverbal memory measures were not significant predictors of the side of seizure focus.

Patterns of treatment response in newly diagnosed epilepsy

PubMed Central

Brodie, M.J.; Barry, S.J.E.; Bamagous, G.A.; Norrie, J.D.

2012-01-01

Objective: To delineate the temporal patterns of outcome and to determine the probability of seizure freedom with successive antiepileptic drug regimens in newly diagnosed epilepsy. Methods: Patients in whom epilepsy was diagnosed and the first antiepileptic drug prescribed between July 1, 1982, and April 1, 2006, were followed up until March 31, 2008. Outcomes were categorized into 4 patterns: A) early and sustained seizure freedom; B) delayed but sustained seizure freedom; C) fluctuation between periods of seizure freedom and relapse; and D) seizure freedom never attained. Probability of seizure freedom with successive drug regimens was compared. Seizure freedom was defined as no seizures for ≥1 year. Results: A total of 1,098 patients were included (median age 32 years, range 9–93). At the last clinic visit, 749 (68%) patients were seizure-free, 678 (62%) on monotherapy. Outcome pattern A was observed in 408 (37%), pattern B in 246 (22%), pattern C in 172 (16%), and pattern D in 272 (25%) patients. There was a higher probability of seizure freedom in patients receiving 1 compared to 2 drug regimens, and 2 compared to 3 regimens (p < 0.001). The difference was greater among patients with symptomatic or cryptogenic than with idiopathic epilepsy. Less than 2% of patients became seizure-free on subsequent regimens but a few did so on their sixth or seventh regimen. Conclusions: Most patients with newly diagnosed epilepsy had a constant course which could usually be predicted early. The chance of seizure freedom declined with successive drug regimens, most markedly from the first to the third and among patients with localization-related epilepsies. PMID:22573629

Measuring functional developmental delay in infants and young children: prevalence rates from the NHIS-D.

PubMed

Simpson, Gloria A; Colpe, Lisa; Greenspan, Stanley

2003-01-01

In order to measure the prevalence of developmental delay among US infants and children, two types of questions were asked of parents in the 1994-95 National Health Interview Survey on Disability (NHIS-D). To measure functional delay (FD), questions from the Functional Developmental Growth Chart (FDQ), which measures specific age-appropriate tasks, were used. General delay (GD) was defined using the general type of questions about developmental delay that had been used in previous surveys. Using a nationally representative sample of 15 291 infants and children aged 4-59 months from the NHIS-D, analyses revealed that, according to these questions, approximately 3.3% had FD and 3.4% of the children had GD. However, only one-third of the children were identified by both sets of questions. Thus, two-thirds of the children identified as having FD were not recognised by their parents as having a delay. Conversely, many parents responded to the GD questions indicating that their child had a delay, but failed to indicate that their child had a functional problem. In addition, only 17% of the children with FD and 31% of those with GD were receiving special services. Multivariable logistic regression analyses found that children with both FD and GD were more likely to be male and to be living in families with incomes below 200% of the poverty level. The findings suggest that the general types of developmental delay questions used in national surveys may not identify children with functional delays. As parents failed to identify these children, it is possible that many of these children may be slipping through paediatric surveillance. Further research to evaluate the use of these measures in population surveys is recommended.

Using Time Delay to Teach Literacy to Students with Severe Developmental Disabilities

ERIC Educational Resources Information Center

Browder, Diane; Ahlgrim-Delzell, Lynn; Spooner, Fred; Mims, Pamela J.; Baker, Joshua N.

2009-01-01

A review of the literature was conducted for articles published between 1975 and 2007 on the application of time delay as an instructional procedure to teach word and picture recognition to students with severe developmental disabilities in an effort to evaluate time delay as an evidence-based practice. A total of 30 experiments were analyzed…

Global developmental delay with sodium valproate-induced gingival hyperplasia.

PubMed

Patil, Ravi B; Urs, Pallavi; Kiran, Shital; Bargale, Seema Dinesh

2014-01-22

Global developmental delay (GDD) refers to a disturbance in an individual child across one or more developmental domains, which include motor, cognition, daily activities, speech and language. The present case discusses a 5-year-old child with GDD associated with infantile spasms treated with sodium valproate. Delay in the widespread acquisition of skills, epilepsy and poor oral hygiene with gingival enlargement was the main concern to seek medical aid. This case is special as the child was suffering from GDD associated with sodium valproate-induced gingival enlargement.

Classifying epileptic EEG signals with delay permutation entropy and Multi-Scale K-means.

PubMed

Zhu, Guohun; Li, Yan; Wen, Peng Paul; Wang, Shuaifang

2015-01-01

Most epileptic EEG classification algorithms are supervised and require large training datasets, that hinder their use in real time applications. This chapter proposes an unsupervised Multi-Scale K-means (MSK-means) MSK-means algorithm to distinguish epileptic EEG signals and identify epileptic zones. The random initialization of the K-means algorithm can lead to wrong clusters. Based on the characteristics of EEGs, the MSK-means MSK-means algorithm initializes the coarse-scale centroid of a cluster with a suitable scale factor. In this chapter, the MSK-means algorithm is proved theoretically superior to the K-means algorithm on efficiency. In addition, three classifiers: the K-means, MSK-means MSK-means and support vector machine (SVM), are used to identify seizure and localize epileptogenic zone using delay permutation entropy features. The experimental results demonstrate that identifying seizure with the MSK-means algorithm and delay permutation entropy achieves 4. 7 % higher accuracy than that of K-means, and 0. 7 % higher accuracy than that of the SVM.

Mutations in KPTN cause macrocephaly, neurodevelopmental delay, and seizures.

PubMed

Baple, Emma L; Maroofian, Reza; Chioza, Barry A; Izadi, Maryam; Cross, Harold E; Al-Turki, Saeed; Barwick, Katy; Skrzypiec, Anna; Pawlak, Robert; Wagner, Karin; Coblentz, Roselyn; Zainy, Tala; Patton, Michael A; Mansour, Sahar; Rich, Phillip; Qualmann, Britta; Hurles, Matt E; Kessels, Michael M; Crosby, Andrew H

2014-01-02

The proper development of neuronal circuits during neuromorphogenesis and neuronal-network formation is critically dependent on a coordinated and intricate series of molecular and cellular cues and responses. Although the cortical actin cytoskeleton is known to play a key role in neuromorphogenesis, relatively little is known about the specific molecules important for this process. Using linkage analysis and whole-exome sequencing on samples from families from the Amish community of Ohio, we have demonstrated that mutations in KPTN, encoding kaptin, cause a syndrome typified by macrocephaly, neurodevelopmental delay, and seizures. Our immunofluorescence analyses in primary neuronal cell cultures showed that endogenous and GFP-tagged kaptin associates with dynamic actin cytoskeletal structures and that this association is lost upon introduction of the identified mutations. Taken together, our studies have identified kaptin alterations responsible for macrocephaly and neurodevelopmental delay and define kaptin as a molecule crucial for normal human neuromorphogenesis. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Three Positive Parenting Practices and Their Correlation with Risk of Childhood Developmental, Social, or Behavioral Delays: An Analysis of the National Survey of Children's Health.

PubMed

Cprek, Sarah E; Williams, Corrine M; Asaolu, Ibitola; Alexander, Linda A; Vanderpool, Robin C

2015-11-01

(1) Investigate the relationship between three specific positive parenting practices (PPP)-reading to children, engaging in storytelling or singing, and eating meals together as a family-and parent-reported risk of developmental, behavioral, or social delays among children between the ages of 1-5 years in the US. (2) Determine if a combination of these parenting practices has an effect on the outcome. Chi square and multiple logistic regression analyses were used to analyze cross-sectional data from the National Survey of Children's Health 2011/2012 in regards to the relationship between each of the three individual PPP as well as a total PPP score and the child's risk of being developmentally, socially, or behaviorally delayed (N = 21,527). Risk of delay was calculated using the Parents' Evaluation of Developmental Status Questionnaire, which is a parental self-report measure that has been correlated with diagnosed child delays. These analyses controlled for poverty and parental education. All analyses were completed using SAS Version 9.3. A strong correlation was found between each of the three PPP as well as the total PPP score and the child's risk of developmental, social, or behavioral delays (p < 0.05 for each test). These associations were found to have a dose-response relationship (p < 0.05 in all but one analysis). Daily engagement in PPP could possibly reduce children's risk of delay, and specifically engaging in all three PPP may have greater benefit.

Semiology of psychogenic nonepileptic seizures: An international cross-cultural study.

PubMed

Asadi-Pooya, Ali A; Valente, Kette; Alessi, Ruda; Tinker, Jennifer

2017-10-01

We compared the semiology of psychogenic nonepileptic seizures (PNES) between patients from the USA and Brazil. This international cross-cultural comparative study may expand understanding of PNES across the borders. We retrospectively investigated all patients with PNES admitted to one epilepsy center in the USA and one in Brazil. We classified their seizures into four classes: generalized motor, akinetic, focal motor, and subjective symptoms. All patients were interviewed by an epileptologist in both countries and were administered psychological assessment measures, including questions about PNES risk factors. For the statistical analyses, we compared patients from the two nations. Eighty-nine patients (49 from the USA and 40 from Brazil) were studied. Patients from the two countries were not significantly different with regard to sex and age, but patients from Brazil had earlier age at onset (26years vs. 34years; P=0.004) and a significantly greater delay in diagnosis (9.9years vs. 5.6years; P=0.001). Some characteristics of PNES were different between the two groups; patients from the USA had generally more seizure types and more often reported subjective seizures (55% in the USA vs. 10% in Brazil; P=0.0001). Clinical and historical characteristics of the patients were not significantly different. Delay in diagnosis of PNES may represent a major factor in resource-limited countries. Large multicenter cross-cultural studies may reveal subtle but significant cross-cultural differences with respect to the semiological, clinical, and historical aspects of PNES; however, patients with PNES share more similarities than differences. Copyright © 2017 Elsevier Inc. All rights reserved.

The inv dup (15) or idic (15) syndrome (Tetrasomy 15q).

PubMed

Battaglia, Agatino

2008-11-19

The inv dup(15) or idic(15) syndrome displays distinctive clinical findings represented by early central hypotonia, developmental delay and intellectual disability, epilepsy, and autistic behaviour. Incidence at birth is estimated at 1 in 30,000 with a sex ratio of almost 1:1. Developmental delay and intellectual disability affect all individuals with inv dup(15) and are usually moderate to profound. Expressive language is absent or very poor and often echolalic. Comprehension is very limited and contextual. Intention to communicate is absent or very limited. The distinct behavioral disorder shown by children and adolescents has been widely described as autistic or autistic-like. Epilepsy with a wide variety of seizure types can occur in these individuals, with onset between 6 months and 9 years. Various EEG abnormalities have been described. Muscle hypotonia is observed in almost all individuals, associated, in most of them, with joint hyperextensibility and drooling. Facial dysmorphic features are absent or subtle, and major malformations are rare. Feeding difficulties are reported in the newborn period.Chromosome region 15q11q13, known for its instability, is highly susceptible to clinically relevant genomic rearrangements, such as supernumerary marker chromosomes formed by the inverted duplication of proximal chromosome 15. Inv dup(15) results in tetrasomy 15p and partial tetrasomy 15q. The large rearrangements, containing the Prader-Willi/Angelman syndrome critical region (PWS/ASCR), are responsible for the inv dup(15) or idic(15) syndrome. Diagnosis is achieved by standard cytogenetics and FISH analysis, using probes both from proximal chromosome 15 and from the PWS/ASCR. Microsatellite analysis on parental DNA or methylation analysis on the proband DNA, are also needed to detect the parent-of-origin of the inv dup(15) chromosome. Array CGH has been shown to provide a powerful approach for identifying and detecting the extent of the duplication. The possible occurrence of double supernumerary isodicentric chromosomes derived from chromosome 15, resulting in partial hexasomy of the maternally inherited PWS/ASCR, should be considered in the differential diagnosis. Large idic(15) are nearly always sporadic. Antenatal diagnosis is possible. Management of inv dup(15) includes a comprehensive neurophysiologic and developmental evaluation. Survival is not significantly reduced.

Automatic seizure detection in SEEG using high frequency activities in wavelet domain.

PubMed

Ayoubian, L; Lacoma, H; Gotman, J

2013-03-01

Existing automatic detection techniques show high sensitivity and moderate specificity, and detect seizures a relatively long time after onset. High frequency (80-500 Hz) activity has recently been shown to be prominent in the intracranial EEG of epileptic patients but has not been used in seizure detection. The purpose of this study is to investigate if these frequencies can contribute to seizure detection. The system was designed using 30 h of intracranial EEG, including 15 seizures in 15 patients. Wavelet decomposition, feature extraction, adaptive thresholding and artifact removal were employed in training data. An EMG removal algorithm was developed based on two features: Lack of correlation between frequency bands and energy-spread in frequency. Results based on the analysis of testing data (36 h of intracranial EEG, including 18 seizures) show a sensitivity of 72%, a false detection of 0.7/h and a median delay of 5.7 s. Missed seizures originated mainly from seizures with subtle or absent high frequencies or from EMG removal procedures. False detections were mainly due to weak EMG or interictal high frequency activities. The system performed sufficiently well to be considered for clinical use, despite the exclusive use of frequencies not usually considered in clinical interpretation. High frequencies have the potential to contribute significantly to the detection of epileptic seizures. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Automatic seizure detection in SEEG using high frequency activities in wavelet domain

PubMed Central

Ayoubian, L.; Lacoma, H.; Gotman, J.

2015-01-01

Existing automatic detection techniques show high sensitivity and moderate specificity, and detect seizures a relatively long time after onset. High frequency (80–500 Hz) activity has recently been shown to be prominent in the intracranial EEG of epileptic patients but has not been used in seizure detection. The purpose of this study is to investigate if these frequencies can contribute to seizure detection. The system was designed using 30 h of intracranial EEG, including 15 seizures in 15 patients. Wavelet decomposition, feature extraction, adaptive thresholding and artifact removal were employed in training data. An EMG removal algorithm was developed based on two features: Lack of correlation between frequency bands and energy-spread in frequency. Results based on the analysis of testing data (36 h of intracranial EEG, including 18 seizures) show a sensitivity of 72%, a false detection of 0.7/h and a median delay of 5.7 s. Missed seizures originated mainly from seizures with subtle or absent high frequencies or from EMG removal procedures. False detections were mainly due to weak EMG or interictal high frequency activities. The system performed sufficiently well to be considered for clinical use, despite the exclusive use of frequencies not usually considered in clinical interpretation. High frequencies have the potential to contribute significantly to the detection of epileptic seizures. PMID:22647836

Seizure ending signs in patients with dyscognitive focal seizures.

PubMed

Gavvala, Jay R; Gerard, Elizabeth E; Macken, Mícheál; Schuele, Stephan U

2015-09-01

Signs indicating the end of a focal seizure with loss of awareness and/or responsiveness but without progression to focal or generalized motor symptoms are poorly defined and can be difficult to determine. Not recognizing the transition from ictal to postictal behaviour can affect seizure reporting accuracy by family members and may lead to delayed or a lack of examination during EEG monitoring, erroneous seizure localization and inadequate medical intervention for prolonged seizure duration. Our epilepsy monitoring unit database was searched for focal seizures without secondary generalization for the period from 2007 to 2011. The first focal seizure in a patient with loss of awareness and/or responsiveness and/or behavioural arrest, with or without automatisms, was included. Seizures without objective symptoms or inadequate video-EEG quality were excluded. A total of 67 patients were included, with an average age of 41.7 years. Thirty-six of the patients had seizures from the left hemisphere and 29 from the right. All patients showed an abrupt change in motor activity and resumed contact with the environment as a sign of clinical seizure ending. Specific ending signs (nose wiping, coughing, sighing, throat clearing, or laughter) were seen in 23 of 47 of temporal lobe seizures and 7 of 20 extra-temporal seizures. Seizure ending signs are often subtle and the most common finding is a sudden change in motor activity and resumption of contact with the environment. More distinct signs, such as nose wiping, coughing or throat clearing, are not specific to temporal lobe onset. A higher proportion of seizures during sleep went unexamined, compared to those during wakefulness. This demonstrates that seizure semiology can be very subtle and arousals from sleep during monitoring should alert staff. Patient accounts of seizure frequency appear to be unreliable and witness reports need to be taken into account. [Published with video sequences].

Developmental profiles and mentality in preschool children with Prader-Willi syndrome: a preliminary study.

PubMed

Chen, Chien-Min; Chen, Chia-Ling; Hou, Jia-Woei; Hsu, Hung-Chih; Chung, Chia-Ying; Chou, Shih-Wei; Lin, Chu-Hsu; Chen, Kai-Hua

2010-01-01

A majority of the children with Prader-Willi syndrome (PWS) have global developmental delay and mental delay. The aim of this study was to investigate the developmental profiles and mental assessments among preschool children with PWS. Ten children with PWS between the ages of 15 months to 6 years, and 11 children with typical development were enrolled. Developmental profiles in terms of their developmental quotient (DQ) for the eight domains of the Chinese Children Developmental Inventory (CCDI) and mental assessments in terms of intelligence quotient (IQ) and developmental index (DI) were carried out for all children. The DQs of all eight domains, including gross motor, fine motor, expressive language, concept comprehension, situation comprehension, self help, personal- social and general development, in the PWS group were lower than the DQs of the children from the typical development group (p < 0.01). Children with PWS had better DQs in the fine motor domain than in the gross motor domain and in the receptive language domain than in the expressive language domain. Furthermore, their verbal IQ were better than their performance IQ and their mental DI was better than their psychomotor DI. These findings suggest that the children with PWS show an uneven global developmental delay together with an uneven mental delay. The results of this study should allow clinicians to better understand the developmental functioning of children with PWS and this will help with the planning of treatment strategies.

Severe developmental delay and multiple strawberry naevi: a new syndrome?

PubMed Central

Upton, C J; Young, I D

1993-01-01

An 18 month old girl with dysmorphic features, severe developmental delay, multiple strawberry naevi, and capillary naevi is described. No previous report of a similar association of features has been identified. Images PMID:8230170

Xenon ventilation during therapeutic hypothermia in neonatal encephalopathy: a feasibility study.

PubMed

Dingley, John; Tooley, James; Liu, Xun; Scull-Brown, Emma; Elstad, Maja; Chakkarapani, Ela; Sabir, Hemmen; Thoresen, Marianne

2014-05-01

Therapeutic hypothermia has become standard of care in newborns with moderate and severe neonatal encephalopathy; however, additional interventions are needed. In experimental models, breathing xenon gas during cooling offers long-term additive neuroprotection. This is the first xenon feasibility study in cooled infants. Xenon is expensive, requiring a closed-circuit delivery system. Cooled newborns with neonatal encephalopathy were eligible for this single-arm, dose-escalation study if clinically stable, under 18 hours of age and requiring less than 35% oxygen. Xenon duration increased stepwise from 3 to 18 hours in 14 subjects; 1 received 25% xenon and 13 received 50%. Respiratory, cardiovascular, neurologic (ie, amplitude-integrated EEG, seizures), and inflammatory (C-reactive protein) effects were examined. The effects of starting or stopping xenon rapidly or slowly were studied. Three matched control subjects per xenon treated subject were selected from our cooling database. Follow-up was at 18 months using mental developmental and physical developmental indexes of the Bayley Scales of Infant Development II. No adverse respiratory or cardiovascular effects, including post-extubation stridor, were seen. Xenon increased sedation and suppressed seizures and background electroencephalographic activity. Seizures sometimes occurred during rapid weaning of xenon but not during slow weaning. C-reactive protein levels were similar between groups. Hourly xenon consumption was 0.52 L. Three died, and 7 of 11 survivors had mental and physical developmental index scores ≥70 at follow-up. Breathing 50% xenon for up to 18 hours with 72 hours of cooling was feasible, with no adverse effects seen with 18 months' follow-up. Copyright © 2014 by the American Academy of Pediatrics.

Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling.

PubMed

Sugaya, Yuki; Kano, Masanobu

2018-05-08

Progress in research on endocannabinoid signaling has greatly advanced our understanding of how it controls neural circuit excitability in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses seizures by inhibiting glutamate release. In contrast, endocannabinoid signaling promotes seizures by inhibiting GABA release at inhibitory synapses. The physiological distribution of endocannabinoid signaling molecules becomes disrupted with the development of epileptic focus in patients with mesial temporal lobe epilepsy and in animal models of experimentally induced epilepsy. Augmentation of endocannabinoid signaling can promote the development of epileptic focus at initial stages. However, at later stages, increased endocannabinoid signaling delays it and suppresses spontaneous seizures. Thus, the regulation of endocannabinoid signaling at specific synapses that cause hyperexcitability during particular stages of disease development may be effective for treating epilepsy and epileptogenesis.

Obstructive sleep apnea syndrome and nocturnal epilepsy with tonic seizures.

PubMed

Bialasiewicz, Piotr; Nowak, Dariusz

2009-12-01

Some ambiguous symptoms may delay or lead to an erroneous diagnosis. We present a case of pure sleep, generalized tonic seizures in a patient with concomitant sleep apnea syndrome. The prolonged apneic periods with tonic muscle contracture lasting minutes and occurring exclusively at night with ensuing confusional state posed diagnostic difficulties because of the negative EEG at the beginning of the workup and the absence of other epilepsy symptoms (i.e. clonic phase, tongue biting, enuresis, seizures while awake). Numerous apneas on polysomnography led to the diagnosis of sleep apnea syndrome. No effect of continuous positive airways pressure (CPAP) treatment on frequency of the nocturnal tonic epileptic fits and the repetitive character of the clinical presentation combined with the typical pathologic changes on subsequent EEGs permitted to suggest the epileptic nature of the paroxysmal events. Episodes stopped following administration of clonazepam. However, spontaneous, coincidental remission of seizures cannot be excluded since the patient remained seizure free even after discontinuation of the drug.

Systemic penicillin as an experimental model of epilepsy.

PubMed

Chen, R C; Huang, Y H; How, S W

1986-06-01

Systemic use of high-dose penicillin was studied in rats and cats to establish an experimental model of epilepsy. In rats, intraperitoneal injection of 2.5 to 5.0 million units/kg (MU/kg) penicillin was effective to induce spikes in 45.7 +/- 31.0 min (means +/- SD) and seizure in 71.5 +/- 38.4 min. In cats, intravenous administration of penicillin at 0.5 to 1.0 MU/kg induced spikes in 10.4 +/- 7.8 min and seizure in 32.2 +/- 19.8 min. Intraperitoneal use of penicillin at 1.0 to 2.0 MU/kg caused spikes in 24.0 +/- 18.4 min and seizure in 71.2 +/- 38.3 min. Pretreatment with intravenous isoniazid at 16.3 +/- 10.3 mg/kg significantly delayed the appearance of intravenous penicillin-induced spikes to 63.1 +/- 49.8 min or prevented the appearance of spikes and abolished the occurrence of seizures. Acupuncture at various points increased the penicillin-induced spikes and seizures.

Developmental delay in moderately preterm-born children with low socioeconomic status: risks multiply.

PubMed

Potijk, Marieke R; Kerstjens, Jorien M; Bos, Arend F; Reijneveld, Sijmen A; de Winter, Andrea F

2013-11-01

To assess separate and joint effects of low socioeconomic status (SES) and moderate prematurity on preschool developmental delay. Prospective cohort study with a community-based sample of preterm- and term-born children (Longitudinal Preterm Outcome Project). We assessed SES on the basis of education, occupation, and family income. The Ages and Stages Questionnaire was used to assess developmental delay at age 4 years. We determined scores for overall development, and domains fine motor, gross motor, communication, problem-solving, and personal-social of 926 moderately preterm-born (MP) (32-36 weeks gestation) and 544 term-born children. In multivariable logistic regression analyses, we used standardized values for SES and gestational age (GA). Prevalence rates for overall developmental delay were 12.5%, 7.8%, and 5.6% in MP children with low, intermediate, and high SES, respectively, and 7.2%, 4.0%, and 2.8% in term-born children, respectively. The risk for overall developmental delay increased more with decreasing SES than with decreasing GA, but the difference was not statistically significant: OR (95% CI) for a 1 standard deviation decrease were: 1.62 (1.30-2.03) and 1.34 (1.05-1.69), respectively, after adjustment for sex, number of siblings, and maternal age. No interaction was found except for communication, showing that effects of SES and GA are mostly multiplicative. Low SES and moderate prematurity are separate risk factors with multiplicative effects on developmental delay. The double jeopardy of MP children with low SES needs special attention in pediatric care. Copyright © 2013 Mosby, Inc. All rights reserved.

Risk factors for death and severe neurological sequelae in childhood bacterial meningitis in sub-Saharan Africa.

PubMed

Pelkonen, Tuula; Roine, Irmeli; Monteiro, Lurdes; Correia, Margarida; Pitkäranta, Anne; Bernardino, Luis; Peltola, Heikki

2009-04-15

We report a morality rate of 33% among 403 children with bacterial meningitis in Angola. A fatal outcome was associated with impaired consciousness, severe dyspnea, and seizures, and severe neurological sequelae (found in 25% of our patients) was associated with delayed presentation to the hospital, impaired consciousness, and seizures. Being underweight was of secondary importance. Treatment with ceftriaxone, rather than with penicillin plus chloramphenicol, did not improve outcome.

Inhibition of GSK3β rescues hippocampal development and learning in a mouse model of CDKL5 disorder.

PubMed

Fuchs, Claudia; Rimondini, Roberto; Viggiano, Rocchina; Trazzi, Stefania; De Franceschi, Marianna; Bartesaghi, Renata; Ciani, Elisabetta

2015-10-01

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in a rare neurodevelopmental disorder characterized by early-onset seizures, severe developmental delay, intellectual disability and Rett syndrome-like features. CDKL5 is highly expressed in the brain during early postnatal stages, suggesting its importance for brain maturation. Using a newly-generated Cdkl5 knockout (Cdkl5 -/Y) mouse, we recently found that loss of Cdkl5 impairs postnatal hippocampal development with a reduction in neuronal precursor survival and maturation. These defects were accompanied by increased activity of the glycogen synthase kinase 3β (GSK3β) a crucial inhibitory regulator of many neurodevelopmental processes. The goal of the current study was to establish whether inhibition of GSK3β corrects hippocampal developmental defects due to Cdkl5 loss. We found that treatment with the GSK3β inhibitor SB216763 restored neuronal precursor survival, dendritic maturation, connectivity and hippocampus-dependent learning and memory in the Cdkl5 -/Y mouse. Importantly, these effects were retained one month after treatment cessation. At present, there are no therapeutic strategies to improve the neurological defects of subjects with CDKL5 disorder. Current results point at GSK3β inhibitors as potential therapeutic tools for the improvement of abnormal brain development in CDKL5 disorder. Copyright © 2015. Published by Elsevier Inc.

Neonatal nonepileptic myoclonus is a prominent clinical feature of KCNQ2 gain-of-function variants R201C and R201H.

PubMed

Mulkey, Sarah B; Ben-Zeev, Bruria; Nicolai, Joost; Carroll, John L; Grønborg, Sabine; Jiang, Yong-Hui; Joshi, Nishtha; Kelly, Megan; Koolen, David A; Mikati, Mohamad A; Park, Kristen; Pearl, Phillip L; Scheffer, Ingrid E; Spillmann, Rebecca C; Taglialatela, Maurizio; Vieker, Silvia; Weckhuysen, Sarah; Cooper, Edward C; Cilio, Maria Roberta

2017-03-01

To analyze whether KCNQ2 R201C and R201H variants, which show atypical gain-of-function electrophysiologic properties in vitro, have a distinct clinical presentation and outcome. Ten children with heterozygous, de novo KCNQ2 R201C or R201H variants were identified worldwide, using an institutional review board (IRB)-approved KCNQ2 patient registry and database. We reviewed medical records and, where possible, interviewed parents and treating physicians using a structured, detailed phenotype inventory focusing on the neonatal presentation and subsequent course. Nine patients had encephalopathy from birth and presented with prominent startle-like myoclonus, which could be triggered by sound or touch. In seven patients, electroencephalography (EEG) was performed in the neonatal period and showed a burst-suppression pattern. However, myoclonus did not have an EEG correlate. In many patients the paroxysmal movements were misdiagnosed as seizures. Seven patients developed epileptic spasms in infancy. In all patients, EEG showed a slow background and multifocal epileptiform discharges later in life. Other prominent features included respiratory dysfunction (perinatal respiratory failure and/or chronic hypoventilation), hypomyelination, reduced brain volume, and profound developmental delay. One patient had a later onset, and sequencing indicated that a low abundance (~20%) R201C variant had arisen by postzygotic mosaicism. Heterozygous KCNQ2 R201C and R201H gain-of-function variants present with profound neonatal encephalopathy in the absence of neonatal seizures. Neonates present with nonepileptic myoclonus that is often misdiagnosed and treated as seizures. Prognosis is poor. This clinical presentation is distinct from the phenotype associated with loss-of-function variants, supporting the value of in vitro functional screening. These findings suggest that gain-of-function and loss-of-function variants need different targeted therapeutic approaches. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

A review of trisomy X (47,XXX).

PubMed

Tartaglia, Nicole R; Howell, Susan; Sutherland, Ashley; Wilson, Rebecca; Wilson, Lennie

2010-05-11

Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). It is the most common female chromosomal abnormality, occurring in approximately 1 in 1,000 female births. As some individuals are only mildly affected or asymptomatic, it is estimated that only 10% of individuals with trisomy X are actually diagnosed. The most common physical features include tall stature, epicanthal folds, hypotonia and clinodactyly. Seizures, renal and genitourinary abnormalities, and premature ovarian failure (POF) can also be associated findings. Children with trisomy X have higher rates of motor and speech delays, with an increased risk of cognitive deficits and learning disabilities in the school-age years. Psychological features including attention deficits, mood disorders (anxiety and depression), and other psychological disorders are also more common than in the general population. Trisomy X most commonly occurs as a result of nondisjunction during meiosis, although postzygotic nondisjunction occurs in approximately 20% of cases. The risk of trisomy X increases with advanced maternal age. The phenotype in trisomy X is hypothesized to result from overexpression of genes that escape X-inactivation, but genotype-phenotype relationships remain to be defined. Diagnosis during the prenatal period by amniocentesis or chorionic villi sampling is common. Indications for postnatal diagnoses most commonly include developmental delays or hypotonia, learning disabilities, emotional or behavioral difficulties, or POF. Differential diagnosis prior to definitive karyotype results includes fragile X, tetrasomy X, pentasomy X, and Turner syndrome mosaicism. Genetic counseling is recommended. Patients diagnosed in the prenatal period should be followed closely for developmental delays so that early intervention therapies can be implemented as needed. School-age children and adolescents benefit from a psychological evaluation with an emphasis on identifying and developing an intervention plan for problems in cognitive/academic skills, language, and/or social-emotional development. Adolescents and adult women presenting with late menarche, menstrual irregularities, or fertility problems should be evaluated for POF. Patients should be referred to support organizations to receive individual and family support. The prognosis is variable, depending on the severity of the manifestations and on the quality and timing of treatment.

A review of trisomy X (47,XXX)

PubMed Central

2010-01-01

Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). It is the most common female chromosomal abnormality, occurring in approximately 1 in 1,000 female births. As some individuals are only mildly affected or asymptomatic, it is estimated that only 10% of individuals with trisomy X are actually diagnosed. The most common physical features include tall stature, epicanthal folds, hypotonia and clinodactyly. Seizures, renal and genitourinary abnormalities, and premature ovarian failure (POF) can also be associated findings. Children with trisomy X have higher rates of motor and speech delays, with an increased risk of cognitive deficits and learning disabilities in the school-age years. Psychological features including attention deficits, mood disorders (anxiety and depression), and other psychological disorders are also more common than in the general population. Trisomy X most commonly occurs as a result of nondisjunction during meiosis, although postzygotic nondisjunction occurs in approximately 20% of cases. The risk of trisomy X increases with advanced maternal age. The phenotype in trisomy X is hypothesized to result from overexpression of genes that escape X-inactivation, but genotype-phenotype relationships remain to be defined. Diagnosis during the prenatal period by amniocentesis or chorionic villi sampling is common. Indications for postnatal diagnoses most commonly include developmental delays or hypotonia, learning disabilities, emotional or behavioral difficulties, or POF. Differential diagnosis prior to definitive karyotype results includes fragile X, tetrasomy X, pentasomy X, and Turner syndrome mosaicism. Genetic counseling is recommended. Patients diagnosed in the prenatal period should be followed closely for developmental delays so that early intervention therapies can be implemented as needed. School-age children and adolescents benefit from a psychological evaluation with an emphasis on identifying and developing an intervention plan for problems in cognitive/academic skills, language, and/or social-emotional development. Adolescents and adult women presenting with late menarche, menstrual irregularities, or fertility problems should be evaluated for POF. Patients should be referred to support organizations to receive individual and family support. The prognosis is variable, depending on the severity of the manifestations and on the quality and timing of treatment. PMID:20459843

Developmental delay

USDA-ARS?s Scientific Manuscript database

Nutrition support is essential for the care of the child with developmental delay. After a thorough evaluation, an individualized intervention plan that accounts for the child’s nutrition status, feeding ability, and medical condition may be determined. Nutrition assessments may be performed at leas...

Slow Spatial Recruitment of Neocortex during Secondarily Generalized Seizures and Its Relation to Surgical Outcome

PubMed Central

Martinet, Louis-Emmanuel; Ahmed, Omar J.; Lepage, Kyle Q.; Cash, Sydney S.

2015-01-01

Understanding the spatiotemporal dynamics of brain activity is crucial for inferring the underlying synaptic and nonsynaptic mechanisms of brain dysfunction. Focal seizures with secondary generalization are traditionally considered to begin in a limited spatial region and spread to connected areas, which can include both pathological and normal brain tissue. The mechanisms underlying this spread are important to our understanding of seizures and to improve therapies for surgical intervention. Here we study the properties of seizure recruitment—how electrical brain activity transitions to large voltage fluctuations characteristic of spike-and-wave seizures. We do so using invasive subdural electrode arrays from a population of 16 patients with pharmacoresistant epilepsy. We find an average delay of ∼30 s for a broad area of cortex (8 × 8 cm) to be recruited into the seizure, at an estimated speed of ∼4 mm/s. The spatiotemporal characteristics of recruitment reveal two categories of patients: one in which seizure recruitment of neighboring cortical regions follows a spatially organized pattern consistent from seizure to seizure, and a second group without consistent spatial organization of activity during recruitment. The consistent, organized recruitment correlates with a more regular, compared with small-world, connectivity pattern in simulation and successful surgical treatment of epilepsy. We propose that an improved understanding of how the seizure recruits brain regions into large amplitude voltage fluctuations provides novel information to improve surgical treatment of epilepsy and highlights the slow spread of massive local activity across a vast extent of cortex during seizure. PMID:26109670

Lesional mesial temporal lobe epilepsy and limited resections: prognostic factors and outcome

PubMed Central

Clusmann, H; Kral, T; Fackeldey, E; Blumcke, I; Helmstaedter, C; von Oertzen, J; Urbach, H; Schramm, J

2004-01-01

Objectives: To evaluate the influence of clinical, investigational, surgical, and histopathological factors on postoperative seizure relief in patients with mesial temporal lobe epilepsy (MTLE) due to lesions other than ammonshornsclerosis (AHS). Methods: Of 738 patients operated for TLE, 78 patients underwent limited resections for lesional MTLE (1990–2000). Seventy four patients with a follow up of more than one year were included. The preoperative clinical, neuropsychological, electroencephalogram, and neuroimaging characteristics were prospectively collected in a database. The histopathological material was re-examined. Results: The mean follow up was 49 months. Fifty eight patients were classified as seizure free (78.4% Class I), and six as almost seizure free (8.1% Class II), grouped together as satisfactory seizure control (64 patients, 86.5%). Five patients (6.8%) were categorised in Classes III and IV, respectively. These were grouped as unsatisfactory seizure control (10 patients, 13.5%). Surgical procedures were: 32 amygdalohippocampectomies (AH), 17 partial anterior AH, 15 AH plus polar resection, seven AH plus basal resection, and three AH plus extended temporal lesionectomy. There was no mortality and 2.7% mild permanent morbidity. Seizure relief did neither differ significantly with these approaches, nor with different classes of pathological findings (43 developmental tumours, 12 glial tumours, 10 dysplasias, and nine others). Even operation of dysplasias resulted in 80% satisfactory seizure control. Seizure onset during childhood proved to be a negative predictor for seizure relief (p = 0.020). MRI revealed 73 suspected lesions (98.6%), one dysembryoplastic neuroepithelial tumour was missed, in four cases no structural abnormalities could be confirmed with histopathological exam. Additionally, multifactorial regression revealed the factors "seizure onset after 10 years of age", "presence of complex partial seizures", "absence of a neurological deficit", and a "correlating neuropsychological deficit" as predictive for satisfactory seizure control. Conclusions: "Preoperative tailoring" resulting in limit resections has proven to be safe and to provide a very good chance for satisfactory seizure relief in patients with lesional MTLE. PMID:15489392

Functional Outcome of School Children With History of Global Developmental Delay.

PubMed

Dornelas, Lílian F; Duarte, Neuza M C; Morales, Nívea M O; Pinto, Rogério M C; Araújo, Renata R H; Pereira, Sílvia A; Magalhães, Lívia C

2016-07-01

This study aimed to investigate the functional and developmental outcomes in school age children diagnosed with global developmental delay before 2 years old and to verify the association between their final diagnosis and environmental and biological factors. Forty-five Brazilian children (26 boys), mean age 95.84 (7.72) months, who attended regular school and were diagnosed with global developmental delay before they were 2 years old had their functions evaluated. Children with global developmental delay were diagnosed with several conditions at school age. Students with greater chances of receiving a diagnosis were those whose mothers were younger at the time their children were born (OR = 1.47, CI = 1.04-2.09, P = .03), who had impaired motor performance, specially balance (OR = 1.33, CI = 1.01-1.75, P = .04), and who needed help during cognitive and behavioral tasks at school (OR = 1.08, CI = 1.00-1.17, P = .048). Interdisciplinary evaluation contributed to defining the specific diagnosis and to identifying the necessity of specialized support. © The Author(s) 2016.

[Diagnostic evaluation of the developmental level in children identified at risk of delay through the Child Development Evaluation Test].

PubMed

Rizzoli-Córdoba, Antonio; Campos-Maldonado, Martha Carmen; Vélez-Andrade, Víctor Hugo; Delgado-Ginebra, Ismael; Baqueiro-Hernández, César Iván; Villasís-Keever, Miguel Ángel; Reyes-Morales, Hortensia; Ojeda-Lara, Lucía; Davis-Martínez, Erika Berenice; O'Shea-Cuevas, Gabriel; Aceves-Villagrán, Daniel; Carrasco-Mendoza, Joaquín; Villagrán-Muñoz, Víctor Manuel; Halley-Castillo, Elizabeth; Sidonio-Aguayo, Beatriz; Palma-Tavera, Josuha Alexander; Muñoz-Hernández, Onofre

The Child Development Evaluation (or CDE Test) was developed in Mexico as a screening tool for child developmental problems. It yields three possible results: normal, slow development or risk of delay. The modified version was elaborated using the information obtained during the validation study but its properties according to the base population are not known. The objective of this work was to establish diagnostic confirmation of developmental delay in children 16- to 59-months of age previously identified as having risk of delay through the CDE Test in primary care facilities. A population-based cross-sectional study was conducted in one Mexican state. CDE test was administered to 11,455 children 16- to 59-months of age from December/2013 to March/2014. The eligible population represented the 6.2% of the children (n=714) who were identified at risk of delay through the CDE Test. For inclusion in the study, a block randomization stratified by sex and age group was performed. Each participant included in the study had a diagnostic evaluation using the Battelle Development Inventory, 2 nd edition. From the 355 participants included with risk of delay, 65.9% were male and 80.2% were from rural areas; 6.5% were false positives (Total Development Quotient ˃90) and 6.8% did not have any domain with delay (Domain Developmental Quotient <80). The proportion of delay for each domain was as follows: communication 82.5%; cognitive 80.8%; social-personal 33.8%; motor 55.5%; and adaptive 41.7%. There were significant differences in the percentages of delay both by age and by domain/subdomain evaluated. In 93.2% of the participants, developmental delay was corroborated in at least one domain evaluated. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Assessment of the usefulness of magnetic resonance brain imaging in patients presenting with acute seizures.

PubMed

Olszewska, D A; Costello, D J

2014-12-01

Magnetic Resonance Imaging (MRI) is increasingly available as a tool for assessment of patients presenting to acute services with seizures. We set out to prospectively determine the usefulness of early MRI brain in a cohort of patients presenting with acute seizures. We examined the MR imaging studies performed in patients admitted solely because of acute seizures to Cork University Hospital over a 12-month period. The main aim of the study was to determine if the MRI established the proximate cause for the patient's recent seizure. We identified 91 patients who underwent MRI brain within 48 h of admission for seizures. Of the 91 studies, 51 were normal (56 %). The remaining 40 studies were abnormal as follows: microvascular disease (usually moderate/severe) (n = 19), post-traumatic gliosis (n = 7), remote symptomatic lesion (n = 6), primary brain tumour (n = 5), venous sinus thrombosis (n = 3), developmental lesion (n = 3), post-surgical gliosis (n = 3) and single cases of demyelination, unilateral hippocampal sclerosis, lobar haemorrhage and metastatic malignant melanoma. Abnormalities in diffusion-weighted sequences that were attributable to prolonged ictal activity were seen in nine patients, all of who had significant ongoing clinical deficits, most commonly delirium. Of the 40 patients with abnormal MRI studies, seven patients had unremarkable CT brain. MR brain imaging revealed the underlying cause for acute seizures in 44 % of patients. CT brain imaging failed to detect the cause of the acute seizures in 19 % of patients in whom subsequent MRI established the cause. This study emphasises the importance of obtaining optimal imaging in people admitted with acute seizures.

Facilitating relational framing in children and individuals with developmental delay using the relational completion procedure.

PubMed

Walsh, Sinead; Horgan, Jennifer; May, Richard J; Dymond, Simon; Whelan, Robert

2014-01-01

The Relational Completion Procedure is effective for establishing same, opposite and comparative derived relations in verbally able adults, but to date it has not been used to establish relational frames in young children or those with developmental delay. In Experiment 1, the Relational Completion Procedure was used with the goal of establishing two 3-member sameness networks in nine individuals with Autism Spectrum Disorder (eight with language delay). A multiple exemplar intervention was employed to facilitate derived relational responding when required. Seven of nine participants in Experiment 1 passed tests for derived relations. In Experiment 2, eight participants (all of whom, except one, had a verbal repertoire) were given training with the aim of establishing two 4-member sameness networks. Three of these participants were typically developing young children aged between 5 and 6 years old, all of whom demonstrated derived relations, as did four of the five participants with developmental delay. These data demonstrate that it is possible to reliably establish derived relations in young children and those with developmental delay using an automated procedure. © Society for the Experimental Analysis of Behavior.

Limited access to special education services for school-aged children with developmental delay.

PubMed

Twardzik, Erica; Smit, Ellen; Hatfield, Bridget; Odden, Michelle C; Dixon-Ibarra, Alicia; MacDonald, Megan

2018-01-01

Current policy in Oregon limits eligibility of children diagnosed with developmental delay for school-based services. Due to eligibility definitions, children with developmental delay may face additional barriers transitioning from early intervention/early childhood special education into school-based special education services. Examine the relationship between enrollment in school-based special education programs given a change in primary disability diagnosis. Logistic regression models were fit for children who enrolled in early intervention/early childhood special education services with a primary disability diagnosis of developmental delay and changed primary disability diagnosis before third grade (n=5076). Odds of enrollment in future special education were greater in children with a change in primary disability diagnosis after the age of five in comparison to children that had a change in primary disability diagnosis before the age of five, while adjusting for demographic characteristics (adjusted odds ratio: 2.37, 95% CI 1.92, 2.92). Results suggest that children who are diagnosed with a developmental delay and exit early childhood special education due to maximum age of eligibility are more likely to enroll in special education compared to children without a gap in service access. Gaps in service access during early development are associated with the need for supportive services later on in life. Copyright © 2017 Elsevier Ltd. All rights reserved.

Three Positive Parenting Practices and Their Correlation with Risk of Childhood Developmental, Social, or Behavioral Delays: An Analysis of the National Survey of Children's Health

PubMed Central

Cprek, Sarah E.; Williams, Corrine M.; Asaolu, Ibitola; Alexander, Linda A.; Vanderpool, Robin C.

2016-01-01

Objectives (1) Investigate the relationship between three specific positive parenting practices (PPP)—reading to children, engaging in storytelling or singing, and eating meals together as a family—and parent-reported risk of developmental, behavioral, or social delays among children between the ages of 1–5 years in the US. (2) Determine if a combination of these parenting practices has an effect on the outcome. Methods Chi square and multiple logistic regression analyses were used to analyze cross-sectional data from the National Survey of Children's Health 2011/2012 in regards to the relationship between each of the three individual PPP as well as a total PPP score and the child's risk of being developmentally, socially, or behaviorally delayed (N = 21,527). Risk of delay was calculated using the Parents’ Evaluation of Developmental Status Questionnaire, which is a parental self-report measure that has been correlated with diagnosed child delays. These analyses controlled for poverty and parental education. All analyses were completed using SAS Version 9.3. Results A strong correlation was found between each of the three PPP as well as the total PPP score and the child's risk of developmental, social, or behavioral delays (p < 0.05 for each test). These associations were found to have a dose–response relationship (p < 0.05 in all but one analysis). Conclusions Daily engagement in PPP could possibly reduce children's risk of delay, and specifically engaging in all three PPP may have greater benefit. PMID:26100132

Developmental Trajectories for Children With Dyslexia and Low IQ Poor Readers

PubMed Central

2016-01-01

Reading difficulties are found in children with both high and low IQ and it is now clear that both groups exhibit difficulties in phonological processing. Here, we apply the developmental trajectories approach, a new methodology developed for studying language and cognitive impairments in developmental disorders, to both poor reader groups. The trajectory methodology enables identification of atypical versus delayed development in datasets gathered using group matching designs. Regarding the cognitive predictors of reading, which here are phonological awareness, phonological short-term memory (PSTM) and rapid automatized naming (RAN), the method showed that trajectories for the two groups diverged markedly. Children with dyslexia showed atypical development in phonological awareness, while low IQ poor readers showed developmental delay. Low IQ poor readers showed atypical PSTM and RAN development, but children with dyslexia showed developmental delay. These divergent trajectories may have important ramifications for supporting each type of poor reader, although all poor readers showed weakness in all areas. Regarding auditory processing, the developmental trajectories were very similar for the two poor reader groups. However, children with dyslexia demonstrated developmental delay for auditory discrimination of Duration, while the low IQ children showed atypical development on this measure. The data show that, regardless of IQ, poor readers have developmental trajectories that differ from typically developing children. The trajectories approach enables differences in trajectory classification to be identified across poor reader group, as well as specifying the individual nature of these trajectories. PMID:27110928

Parenting Practices and Associations with Development Delays among Young Children in Dominican Republic.

PubMed

Uwemedimo, Omolara Thomas; Howlader, Afrin; Pierret, Giselina

According to the World Health Organization, >200 million children in low- and middle-income countries experience developmental delays. However, household structure and parenting practices have been minimally explored as potential correlates of developmental delay in low- and middle-income countries, despite potential as areas for intervention. The objective of the study was to examine associations of developmental delays with use of World Health Organization-recommended parenting practices among a clinic-based cohort of children aged 6-60 months attending in La Romana, Dominican Republic. This study was conducted among 74 caregiver-child pairs attending the growth-monitoring clinic at Hospital Francisco Gonzalvo in June 2015. The Malawi Developmental Assessment Tool was adapted and performed on each child to assess socioadaptive, fine motor, gross motor, and language development. The IMCI Household Level Survey Questionnaire was used to assess parenting practices. Fisher's exact test was used to determine associations significant at P < .05. Significant variables were then entered into a multivariable logistic regression. Almost two-thirds of children had a delay in at least 1 developmental domain. Most caregivers used scolding (43.2%) or spanking (44%) for child discipline. Children who were disciplined by spanking and scolding were more likely to have language delay (P = .007) and socioadaptive delay (P = .077), respectively. On regression analysis, children with younger primary caregivers had 7 times higher odds of language delay (adjusted odds ratio [AOR]: 7.35, 95% confidence interval [CI]: 1.52-35.61) and 4 times greater odds of any delay (AOR: 4.72, 95% CI: 1.01-22.22). In addition, children punished by spanking had 5 times higher odds of having language delay (AOR: 5.04, 95% CI: 1.13-22.39). Parenting practices such as harsh punishment and lack of positive parental reinforcement were found to have strong associations with language and socioadaptive delays. Likewise, delays were also more common among children with younger caregivers. Copyright © 2017 Icahn School of Medicine at Mount Sinai. Published by Elsevier Inc. All rights reserved.

Focus on ECT seizure quality: serum BDNF as a peripheral biomarker in depressed patients.

PubMed

Bumb, Jan Malte; Aksay, Suna Su; Janke, Christoph; Kranaster, Laura; Geisel, Olga; Gass, Peter; Hellweg, Rainer; Sartorius, Alexander

2015-04-01

Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment in severest or drug-resistant affective disorders. The potential relation between any peripheral biological marker and the seizure quality as a surrogate for treatment efficacy has not been investigated so far. We prospectively examined serum brain-derived neurotrophic factor (BDNF) levels in 20 patients with major depression before and after electroconvulsive therapy. A seizure quality sum score for every ECT session was build up on the basis of the seizure duration, seizure amplitude, central inhibition, interhemispheric coherence and sympathetic activation. Serum BDNF levels were significantly higher after ECT (P = 0.036). In the linear regression analysis, a significant correlation of the serum BDNF levels and the time between the last ECT and the blood withdrawal (P = 0.01) was observed. The ANOVA revealed a significant influence of the interval between the last ECT and the blood withdrawal (P = 0.0017) as well as the seizure quality (P = 0.038) on the variance of BDNF serum levels. Our data corroborate the neurotrophin hypothesis suggesting an ECT-induced central BDNF rise leading to a delayed (>6 days) and increased equilibrium of the peripheral BDNF. The association of seizure adequacy with a BDNF rise might underline the importance of monitoring seizure quality markers in daily practice.

Risk and protective factors in early child development: Results from the All Our Babies (AOB) pregnancy cohort.

PubMed

McDonald, Sheila; Kehler, Heather; Bayrampour, Hamideh; Fraser-Lee, Nonie; Tough, Suzanne

2016-11-01

Understanding factors that protect against early developmental delay among children who are experiencing adversity can inform prevention and early intervention strategies. To identify risk factors for development delay at one year and protective factors for developmental delay in 'at risk' environments (poor maternal mental health and socio-demographic risk). Data was analyzed from 3360 mother-child dyads who participated in the All Our Babies (AOB) pregnancy cohort. Participants completed four questionnaires spanning pregnancy to one year postpartum and provided access to medical records. Risk factors for developmental delay at age one were identified using bivariate methods and multivariable modeling. Protective factors for child development in 'at risk' family environments were identified using bivariate analyses. At one year, 17% of children were developmentally delayed, defined as scoring in the monitoring zone on at least 2 of the 5 developmental domains of the Ages and Stages Questionnaire. Prenatal depression, preterm birth, low community engagement, and non-daily parent-child interaction increased the risk of delay. Protective factors for children in 'at risk' environments included relationship happiness, parenting self-efficacy, community engagement, higher social support, and daily parent-child interaction. The study results suggest that maternal and infant outcomes would be improved, even for vulnerable women, through identification and intervention to address poor mental health and through normalizing engagement with low cost, accessible community resources that can also support parent-child interaction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Validity of false belief tasks in blind children.

PubMed

Brambring, Michael; Asbrock, Doreen

2010-12-01

Previous studies have reported that congenitally blind children without any additional impairment reveal a developmental delay of at least 4 years in perspective taking based on testing first-order false-belief tasks. These authors interpret this delay as a sign of autism-like behavior. However, the delay may be caused by testing blind children with false-belief tasks that require visual experience. Therefore, the present study gave alternative false-belief tasks based on tactile or auditory experience to 45 congenitally blind 4-10-year-olds and 37 sighted 3-6-year-olds. Results showed criterion performance at 80 months (6; 8 years) in blind children compared with 61 months (5; 1 years) in sighted controls. It is concluded that this 19-month (1; 7 year) difference, which is comparable with delays in other developmental areas, is a developmental delay caused by the fact of congenital blindness rather than a sign of a psychopathological disorder of autism-like behavior.

Effects of tianeptine on onset time of pentylenetetrazole-induced seizures in mice: possible role of adenosine A1 receptors.

PubMed

Uzbay, Tayfun I; Kayir, Hakan; Ceyhan, Mert

2007-02-01

Depression is a common psychiatric problem in epileptic patients. Thus, it is important that an antidepressant agent has anticonvulsant activity. This study was organized to investigate the effects of tianeptine, an atypical antidepressant, on pentylenetetrazole (PTZ)-induced seizure in mice. A possible contribution of adenosine receptors was also evaluated. Adult male Swiss-Webster mice (25-35 g) were subjects. PTZ (80 mg/kg, i.p.) was injected to mice 30 min after tianeptine (2.5-80 mg/kg, i.p.) or saline administration. The onset times of 'first myoclonic jerk' (FMJ) and 'generalized clonic seizures' (GCS) were recorded. Duration of 600 s was taken as a cutoff time in calculation of the onset time of the seizures. To evaluate the contribution of adenosine receptors in the effect of tianeptine, a nonspecific adenosine receptor antagonist caffeine, a specific A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a specific A2A receptor antagonist 8-(3-chlorostyryl) caffeine (CSC) or their vehicles were administered to the mice 15 min before tianeptine (80 mg/kg) or saline treatments. Tianeptine (40 and 80 mg/kg) pretreatment significantly delayed the onset time of FMJ and GCS. Caffeine (10-60 mg/kg, i.p.) dose-dependently blocked the retarding effect of tianeptine (80 mg/kg) on the onset times of FMJ and GCS. DPCPX (20 mg/kg) but not CSC (1-8 mg/kg) blocked the effect of tianeptine (80 mg/kg) on FMJ. Our results suggest that tianeptine delayed the onset time of PTZ-induced seizures via adenosine A1 receptors in mice. Thus, this drug may be a useful choice for epileptic patients with depression.

Evidence-based guideline: Management of an unprovoked first seizure in adults

PubMed Central

Krumholz, Allan; Wiebe, Samuel; Gronseth, Gary S.; Gloss, David S.; Sanchez, Ana M.; Kabir, Arif A.; Liferidge, Aisha T.; Martello, Justin P.; Kanner, Andres M.; Shinnar, Shlomo; Hopp, Jennifer L.; French, Jacqueline A.

2015-01-01

Objective: To provide evidence-based recommendations for treatment of adults with an unprovoked first seizure. Methods: We defined relevant questions and systematically reviewed published studies according to the American Academy of Neurology's classification of evidence criteria; we based recommendations on evidence level. Results and recommendations: Adults with an unprovoked first seizure should be informed that their seizure recurrence risk is greatest early within the first 2 years (21%–45%) (Level A), and clinical variables associated with increased risk may include a prior brain insult (Level A), an EEG with epileptiform abnormalities (Level A), a significant brain-imaging abnormality (Level B), and a nocturnal seizure (Level B). Immediate antiepileptic drug (AED) therapy, as compared with delay of treatment pending a second seizure, is likely to reduce recurrence risk within the first 2 years (Level B) but may not improve quality of life (Level C). Over a longer term (>3 years), immediate AED treatment is unlikely to improve prognosis as measured by sustained seizure remission (Level B). Patients should be advised that risk of AED adverse events (AEs) may range from 7% to 31% (Level B) and that these AEs are likely predominantly mild and reversible. Clinicians' recommendations whether to initiate immediate AED treatment after a first seizure should be based on individualized assessments that weigh the risk of recurrence against the AEs of AED therapy, consider educated patient preferences, and advise that immediate treatment will not improve the long-term prognosis for seizure remission but will reduce seizure risk over the subsequent 2 years. PMID:25901057

Focal seizure symptoms in idiopathic generalized epilepsies.

PubMed

Seneviratne, Udaya; Woo, Jia J; Boston, Ray C; Cook, Mark; D'Souza, Wendyl

2015-08-18

We sought to study the frequency and prognostic value of focal seizure symptoms (FSS) in idiopathic generalized epilepsies (IGE) using a validated tool: Epilepsy Diagnostic Interview Questionnaire and Partial Seizure Symptom Definitions. Participants with IGE were recruited from epilepsy clinics at 2 tertiary hospitals. The diagnosis was validated and classified into syndromes according to the International League Against Epilepsy criteria by 2 epileptologists independently with discordance resolved by consensus. The Epilepsy Diagnostic Interview Questionnaire utilizes both open- and closed-ended questions to elicit FSS in association with generalized tonic-clonic seizures, myoclonus, and absences. The elicited FSS were classified according to the Partial Seizure Symptom Definitions. Regression analysis was conducted to examine the relationship between the duration of seizure freedom and FSS. A total of 135 patients were studied, of whom 70 (51.9%) reported FSS. Those symptoms occurred in association with generalized tonic-clonic seizures (53.1%) as well as myoclonus and absences (58%). FSS were reported with similar frequency in juvenile absence epilepsy (62.5%) and juvenile myoclonic epilepsy (60%), and with a lesser frequency in generalized epilepsy with tonic-clonic seizures only (39.5%) and childhood absence epilepsy (33.3%). A strong relationship between FSS and duration of seizure freedom was found (regression coefficient -0.665, p = 0.037). FSS are frequently reported by patients with IGE. A shorter duration of seizure freedom is associated with FSS. Recognition of the presence of FSS in IGE is important to avoid misdiagnosis and delayed diagnosis as well as to choose appropriate antiepileptic drug therapy. © 2015 American Academy of Neurology.

[Clinical characteristics and prognosis analysis of vitamin B6 responsive infantile spasms].

PubMed

Xue, Jiao; Yang, Zhixian; Wu, Ye; Xiong, Hui; Zhang, Yuehua; Liu, Xiaoyan

2016-02-01

To analyze clinical characteristics, treatment and prognosis in a cohort of children with vitamin B6 responsive infantile spasms. Ten patients were diagnosed as vitamin B6 responsive infantile spasms in Peking University First Hospital between January 2012 and May 2015.The clinical manifestations, diagnosis and treatment process, video-electroencephalogram, magnetic resonance imaging (MRI), epilepsy related genes and prognosis were retrospectively analyzed. Of the 10 patients, 5 were male, and 5 were female. Eight of them were normal at birth, and the other 2 patients had intracranial hemorrhage or anoxia.The age of epilepsy onset was from 3.5 to 8.0 months.All patients presented spasms primarily.Interictal electroencephalogram (EEG) showed hypsarrhythmia at seizures onset. MRI showed normal in 8 patients, and subarachnoid hemorrhage or multiple encephalomalacia foci after hemorrhage respectively in the other 2 patients. The results of blood biochemical, cerebrospinal fluid examination and urinary metabolic screening were negative. Epilepsy related genes including ALDH7A1 gene analysis showed wild type in all patients. Two patients were classified as symptomatic and eight might be idiopathic or cryptogenic. The initial dose of vitamin B6 was 10.0 mg/(kg·d). The interval between seizures onset and taking vitamin B6 was 0 to 4.0 months. Seizures disappeared completely within a week after administration of vitamin B6 in 9 patients and in 1.5 months in one patient.Of the 8 patients whose seizures were controlled completely during the follow-up period, 7 patients' EEG recovered within 1.5 to 4.0 months and then continued to be normal. The EEG of the rest of a patient returned to normal, but showed abnormal discharges after stopping taking vitamin B6. Two patients' EEG continued abnormal and seizures recurred due to vitamin B6 withdrawal. At the last follow-up, seizures were controlled in all patients. Drug treatment in one case had stopped. Vitamin B6 was used in 9 patients at a dose of 0.4 to 10.0 mg/(kg·d). Among them, vitamin B6 monotherapy or coadministration with one low dose antiepileptic drug was applied in 6 or 3 patients respectively. The psychomotor development was normal in 5 patients, mild delay in 3 patients, and severe delay in 2 patients with autism behavior. Of the 2 symptomatic patients, one developed normally and the other showed severe delay. Vitamin B6 might have effects on both idiopathic or cryptogenic and symptomatic patients, especially for the former. High dose vitamin B6 should be first tried in all patients with infantile spasms. Patients who had response to vitamin B6 could be controlled within a short time and might have better outcomes. Seizures were not easy to relapse in those whose seizures were controlled and EEG recovered completely. Vitamin B6 could be gradually reduced during the course and might be withdrawn in the future. The recurrence of seizures was closely related to EEG abnormality.

Chronic Disease and Perceived Developmental Progression in Adolescence.

ERIC Educational Resources Information Center

Seiffge-Krenke, Inge

1998-01-01

Examined whether chronic illness causes delays in adolescents' perceived developmental status, using annually-completed questionnaires from insulin-dependent and healthy adolescents. Found that, in first year of study, diabetic adolescents reported delays in physical maturity and an independent lifestyle compared with healthy peers. Overall…

Inclusive intervention to enhance the fundamental movement skills of children without hearing: a preliminary study.

PubMed

Gursel, Ferda

2014-02-01

The purpose of this study was to assess an intervention program on the fundamental movement skill of students with and without hearing impairment, using the Test of Gross Motor Development-2 (TGMD-2) standardized Turkish norm. Preschool children with and without hearing impairment participated in this study. At the beginning of the study, most of the children with hearing impairment demonstrated developmental delay on the Locomotor subscale (6/7), as did about one-third (4/11) of the children without hearing impairment. For the Object control subscale, 4/7 of children with hearing impairment and none without hearing impairment showed developmental delay prior to the intervention program. After the intervention program, 3/7 children with hearing impairment had developmental delay on the Locomotor subscale. On the Object control subscale, 2/7 children with hearing impairment and none without hearing impairment showed developmental delay. The six-week intervention program improved TGMD-2 scores of children with hearing impairment, yet did not yield statistically significant improvement of fundamental movement skills.

Education on the Brain: A Partnership Between a Pediatric Primary Care Center and Neurology Residency.

PubMed

Zwemer, Eric; Bernson-Leung, Miya; Rea, Corinna; Patel, Archana A; Guerriero, Rejean; Urion, David K; Toomey, Sara L

2018-01-01

The national shortage of pediatric neurologists is worsening, yet referral rates by pediatricians are high. Suboptimal training of pediatric residents in care of patients with neurologic disease may be a contributing factor. We formed a partnership between the Boston Children's Primary Care at Longwood clinic and Child Neurology Residency Training Program. The educational intervention included lectures, observed neurologic examinations, in-person and virtual triage, and an electronic medical record-based consult system. Residents in other primary care clinics served as the comparison group. Intervention-group residents reported significantly improved confidence in diagnosis of chronic/recurrent headache, attention deficit hyperactivity disorder (ADHD), and developmental delay; initial management of ADHD and developmental delay; and secondary management of ADHD, developmental delay, and concussion/traumatic brain injury. Comparison-group residents reported significantly improved confidence only in diagnosis of developmental delay. Our multipronged intervention is a promising approach to improving pediatric resident training in pediatric neurology and may be generalizable to subspecialty collaborations for other residency programs.

The differences in clinical aspect between specific language impairment and global developmental delay.

PubMed

Kim, Seong Woo; Jeon, Ha Ra; Park, Eun Ji; Chung, Hee Jung; Song, Jung Eun

2014-12-01

To compare and analyze the clinical characteristics of children with delayed language acquisition due to two different diagnoses, which were specific language impairment (SLI, a primarily delayed language development) and global developmental delay (GDD, a language delay related to cognitive impairment). Among 1,598 children who had visited the developmental delay clinic from March 2005 to February 2011, 467 children who were diagnosed with GDD and 183 children who were diagnosed with SLI were included in this study. All children were questioned about past, family, and developmental history, and their language competences and cognitive function were assessed. Some children got electroencephalography (EEG), in case of need. The presence of the perinatal risk factors showed no difference in two groups. In the children with GDD, they had more delayed acquisition of independent walking and more frequent EEG abnormalities compared with the children with SLI (p<0.01). The positive family history of delayed language development was more prevalent in children with SLI (p<0.01). In areas of language ability, the quotient of receptive language and expressive language did not show any meaningful statistical differences between the two groups. Analyzing in each group, the receptive language quotient was higher than expressive language quotient in both group (p<0.01). In the GDD group, the Bayley Scales of Infant Development II (BSID-II) showed a marked low mental and motor quotient while the Wechsler Intelligence Scale showed low verbal and nonverbal IQ. In the SLI group, the BSID-II and Wechsler Intelligence Scale showed low scores in mental area and verbal IQ but sparing motor area and nonverbal IQ. The linguistic profiles of children with language delay could not differentiate between SLI and GDD. The clinicians needed to be aware of these developmental issues, and history taking and clinical evaluation, including cognitive assessment, could be helpful to diagnose adequately and set the treatment plan for each child.

Accelerated long-term forgetting in children with temporal lobe epilepsy.

PubMed

Gascoigne, Michael B; Smith, Mary Lou; Barton, Belinda; Webster, Richard; Gill, Deepak; Lah, Suncica

2014-07-01

Adults with temporal lobe epilepsy (TLE) have been found to have accelerated long-term forgetting, but this phenomenon has not yet been investigated in children. Although deficits in recall of materials after short (20- to 30-minute) delays have been shown to slowly emerge from childhood to adolescence in patients with TLE, it is unknown whether such a trend will also be found in recall of materials after long delays. This study examined the presence of accelerated long-term forgetting in children with TLE and how it relates to chronological age. Twenty-three children with TLE and 58 healthy controls of similar age, sex distribution and socioeconomic status completed a battery of neuropsychological tests, including standardised tests of story recall and design location, as well as two experimental tests requiring the learning of words and design locations to a criterion, both of which assessed recall after short (30-min) and long (7-day) delays. Word recall at the 7-day delay (relative to the 30-min recall) was significantly poorer in the TLE group, compared to the control group. The TLE group also exhibited worse 30-min recall performance on a standardised test of story recall. Individual patient analyses revealed dissociation between performance on the experimental and standardised verbal memory tests; children who were impaired on the experimental test (7-day delay) were not impaired on the standardised test (30-min delay). Compared to controls, patients with a left-hemisphere seizure focus recalled fewer words at short and long delays while patients with an abnormal hippocampus recalled fewer words at the long delay. No between-group differences were found with respect to the design location task. Age negatively correlated with the recall of words after short- and long-term delays within the TLE group, where older age was associated with worse memory. This association was not present in the control group. To our knowledge, this is the first study to show evidence of accelerated long-term forgetting in children with TLE, which could not be explained by poor performance on standardised memory tests. Additionally, these results suggest that the developmental trajectory of long-term memory in children with TLE is similar to that of short-term memory: deficits emerge gradually, therefore older children are more likely to present with long-term memory deficits. Copyright © 2014 Elsevier Ltd. All rights reserved.

CDC Kerala 5: Developmental therapy clinic experience--use of Child Development Centre grading for motor milestones.

PubMed

Nair, M K C; Resmi, V R; Krishnan, Rajee; Harikumaran Nair, G S; Leena, M L; Bhaskaran, Deepa; George, Babu; Russell, Paul Swamidhas Sudhakar

2014-12-01

To document the experiences of the intervention given to children who attended the developmental therapy clinic of Child Development Centre (CDC) Kerala, a specialized clinic for providing developmental intervention/therapy for babies less than two years with developmental delay/disability. All the babies referred to this speciality clinic from developmental screening/evaluation clinics of CDC were registered in the clinic and re-evaluation was done using CDC grading for head holding, sitting, standing, Amiel Tison passive angles, and Trivandrum Developmental Screening Chart (TDSC) 0-2 y. Out of a total of 600 consecutive babies below 2 y with developmental delay/disability referred to developmental therapy clinic, on comparing the test results at enrollment and after 6 mo of intervention, a statistically significant reduction was observed (i) in the 2-4 mo age group with regard to abnormal TDSC (25.5%), (ii) in the 4-8 mo age group with regard to abnormal head holding grade (87.1%) and abnormal TDSC (19.4%), (iii) in the 8-12 mo age group, with regard to abnormal sitting grade (71.7%) and (iv) in the above 12 mo age group with regard to abnormal sitting grade (35.3%) and abnormal standing grade (78.8%). The experience of organizing the developmental intervention/therapy clinic at CDC Kerala has shown that therapy services by developmental therapists in a centre and supportive therapy by mother at home is useful in improving the developmental status of children with developmental delay.

Seizure semiology and electroencephalography in young children with lesional temporal lobe epilepsy.

PubMed

Lv, Rui-Juan; Sun, Zhen-Rong; Cui, Tao; Shao, Xiao-Qiu

2014-02-01

This study aimed to discuss the clinical features of seizure semiology and electroencephalography (EEG) in young children with lesional temporal lobe epilepsy (TLE). Children with lesional TLE received presurgical evaluation for intractable epilepsy. They were followed up for more than one year after temporal lobectomy. We reviewed the medical history and video-EEG monitoring of children with TLE to analyze the semiology of seizures and EEG findings and compared the semiology of seizures and EEG findings of childhood TLE and adult TLE. A total of 84 seizures were analyzed in 11 children (aged 23-108 months). The age of seizure onset was from 1 month to 26 months (a mean of 17.6 months). All of the patients exhibited prominent motor manifestations including epileptic spasm, tonic seizure, and unilateral clonic seizure. Seven children manifested behavioral arrest similar to an automotor seizure in adult TLE but with a shorter duration and higher frequency. The automatisms were typically orofacial, whereas manual automatisms were rarely observed. The EEG recordings revealed that diffuse discharge patterns were more common in younger children, whereas focal or unilateral patterns were more typical in older children. All of the patients were seizure-free after temporal lobectomy with more than one-year follow-up. All of the children had a mental development delay or regression; however, there was improvement after surgery, especially in those with surgery performed early. In contrast to TLE in adults, young children with lesional TLE probably represent a distinct nosological and probably less homogeneous syndrome. Although they had generalized clinical and electrographic features, resective epilepsy surgery should be considered as early as possible to obtain seizure control and improvement in mental development. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

A Mobile Early Stimulation Program to Support Children with Developmental Delays in Brazil.

PubMed

Dias, Raquel da Luz; Silva, Kátia Cristina Correa Guimarães; Lima, Marcela Raquel de Oliveira; Alves, João Guilherme Bezerra; Abidi, Syed Sibte Raza

2018-01-01

Developmental delay is a deviation development from the normative milestones during the childhood and it may be caused by neurological disorders. Early stimulation is a standardized and simple technique to treat developmental delays in children (aged 0-3 years), allowing them to reach the best development possible and to mitigate neuropsychomotor sequelae. However, the outcomes of the treatment depending on the involvement of the family, to continue the activities at home on a daily basis. To empower and educate parents of children with neurodevelopmental delays to administer standardized early stimulation programs at home, we developed a mobile early stimulation program that provides timely and evidence-based clinical decision support to health professionals and a personalized guidance to parents about how to administer early stimulation to their child at home.

Expanding the phenotype of Triple X syndrome: A comparison of prenatal versus postnatal diagnosis.

PubMed

Wigby, Kristen; D'Epagnier, Cheryl; Howell, Susan; Reicks, Amy; Wilson, Rebecca; Cordeiro, Lisa; Tartaglia, Nicole

2016-11-01

Triple X syndrome (47, XXX) occurs in approximately 1:1,000 female births and has a variable phenotype of physical and psychological features. Prenatal diagnosis rates of 47, XXX are increasing due to non-invasive prenatal genetic testing. Previous studies suggest that prenatal diagnosed females have better neurodevelopmental outcomes. This cross-sectional study describes diagnosis, physical features, medical problems, and neurodevelopmental features in a large cohort of females with 47, XXX. Evaluation included review of medical and developmental history, physical exam, cognitive, and adaptive testing. Medical and developmental features were compared between the prenatal and postnatal diagnosis groups using rate calculations and Fisher's exact test. Cognitive and adaptive tests scores were compared using t-tests. Seventy-four females age 6 months-24 years (mean 8.3 years) participated. Forty-four (59.5%) females were in the prenatal diagnosis group. Mean age of postnatal diagnosis was 5.9 years; developmental delay was the most common indication for postnatal genetic testing. Common physical features included hypertelorism, epicanthal folds, clinodactyly, and hypotonia. Medical problems included dental disorders (44.4%), seizure disorders (16.2%), genitourinary malformations (12.2%). The prenatal diagnosis group had higher verbal (P < 0.001), general ability index (P = 0.004), and adaptive functioning scores (P < 0.001). Rates of ADHD (52.2% vs. 45.5%, P = 0.77) and learning disabilities (39.1% vs. 36.3%, P = 1.00) were similar between the two groups. These findings expand on the phenotypic features in females with Triple X syndrome and support that prenatally ascertained females have better cognitive and functional outcomes. However, prenatally diagnosed females are still at risk for neurodevelopmental disorders. Genetic counseling and treatment recommendations are summarized. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

34 CFR 303.111 - State definition of developmental delay.

Code of Federal Regulations, 2013 CFR

2013-07-01

... child's development; and (b) Specify the level of developmental delay in functioning or other comparable... INFANTS AND TODDLERS WITH DISABILITIES State Eligibility for a Grant and Requirements for a Statewide... to appropriately identify infants and toddlers with disabilities who are in need of services under...

34 CFR 303.111 - State definition of developmental delay.

Code of Federal Regulations, 2014 CFR

2014-07-01

... child's development; and (b) Specify the level of developmental delay in functioning or other comparable... INFANTS AND TODDLERS WITH DISABILITIES State Eligibility for a Grant and Requirements for a Statewide... to appropriately identify infants and toddlers with disabilities who are in need of services under...

34 CFR 303.111 - State definition of developmental delay.

Code of Federal Regulations, 2012 CFR

2012-07-01

... child's development; and (b) Specify the level of developmental delay in functioning or other comparable... INFANTS AND TODDLERS WITH DISABILITIES State Eligibility for a Grant and Requirements for a Statewide... to appropriately identify infants and toddlers with disabilities who are in need of services under...

Novel homozygous missense mutation in ALDH7A1 causes neonatal pyridoxine dependent epilepsy.

PubMed

Coci, Emanuele G; Codutti, Luca; Fink, Christian; Bartsch, Sophie; Grüning, Gunnar; Lücke, Thomas; Kurth, Ingo; Riedel, Joachim

2017-04-01

Pyridoxine dependent epilepsy (PDE) (OMIM#266100) is a neonatal form of epilepsy, caused by dysfunction of the enzyme α-aminoadipic semialdehyde dehydrogenase (ALDH7A1 or Antiquitin). This enzyme converts α-aminoadipic semialdehyde (α-AASA) into α-aminoadipate (AAA), a critical step in the lysine metabolism of the brain. ALDH7A1 dysfunction causes an accumulation of α-AASA and δ 1 -piperideine-6-carboxylic acid (P6C), which are in equilibrium with each other. P6C binds and inactivates pyridoxal 5'-phosphate (PLP), the active form of pyridoxine. Individuals affected by ALDH7A1 deficiency show pre-natal and post-natal seizures, which respond to oral pyridoxine but not to other pediatric anti-epileptic drugs. We discovered a novel missense mutation (c.566G > A, p.Gly189Glu) in homozygous state residing in the NAD+ binding domain coding region of exon 6 and affecting an highly conserved amino acid residue. The seizures stopped under post-natal pyridoxine therapy, nevertheless a longer follow-up is needed to evaluate the intellectual development of the child, who is additionally treated with oral l-arginine since the 13th month of life. Developmental delay with or without structural cortex abnormalities were reported in several patients. A brain MRI scan revealed hyperintense white matter in the right cerebellum compatible with cerebellar gliosis. Taken together, our studies enlarge the group of missense pathogenic mutations of ALDH7A1 gene and reveal a novel cerebellar finding within the PDE patients cohort. Copyright © 2016 Elsevier Ltd. All rights reserved.

Global development and adaptive behaviour in children with early-onset epilepsy: a population-based case-control study.

PubMed

Reilly, Colin; Atkinson, Patricia; Memon, Ayesha; Jones, Chloe; Dabydeen, Lyvia; Das, Krishna B; Gillberg, Christopher; Neville, Brian G R; Mahoney, J Matthew; Scott, Rod C

2018-06-03

There are limited population-based data on global development and adaptive behaviour in children with early-onset epilepsy. The aims of this study were: (1) to identify the prevalence of deficits in global development and adaptive behaviour experienced by children with early-onset epilepsy; (2) to identify factors associated with such deficits; and (3) to compare the relationship between measures of neurodevelopment in the group with epilepsy to a group without epilepsy who had other neurological or neurodevelopmental difficulties. The Sussex Early Epilepsy and Neurobehaviour study is a prospective, community-based study involving children (1-7y) with epilepsy. We undertook comprehensive psychological assessment with participants, including measures of global development and adaptive behaviour. We compared the children with epilepsy with a sex, age, and developmentally-matched group of children without epilepsy who had neurodevelopmental or neurological difficulties using correlation matrices. Forty-eight children (91% of the eligible population) with epilepsy underwent assessment. Seventy-one per cent of children displayed delayed global development (<2SD) and 56% showed significant deficits (<2SD) in adaptive behaviour. Our analysis revealed that non-white ethnicity and use of polytherapy were independently associated with decreased scores on measures of global development and adaptive behaviour. The correlations between measures of developmental functioning were higher in children with epilepsy than in those without. Children with early-onset epilepsy frequently have difficulties with global development and adaptive behaviour. The higher correlations between neurodevelopmental measures in children with epilepsy suggest that the profile in children with epilepsy is different. This may have significant implications for both neuropathology and interventions. Children with early-onset epilepsy are at significant risk of intellectual disability. Developmental impairment is associated with use of polytherapy but not with any seizure parameters. Developmental profiles in young children with epilepsy differ from other conditions. © 2018 Mac Keith Press.

Neonatal seizures alter NMDA glutamate receptor GluN2A and 3A subunit expression and function in hippocampal CA1 neurons

PubMed Central

Zhou, Chengwen; Sun, Hongyu; Klein, Peter M.; Jensen, Frances E.

2015-01-01

Neonatal seizures are commonly caused by hypoxic and/or ischemic injury during birth and can lead to long-term epilepsy and cognitive deficits. In a rodent hypoxic seizure (HS) model, we have previously demonstrated a critical role for seizure-induced enhancement of the AMPA subtype of glutamate receptor (GluA) in epileptogenesis and cognitive consequences, in part due to GluA maturational upregulation of expression. Similarly, as the expression and function of the N-Methyl-D-aspartate (NMDA) subtype of glutamate receptor (GluN) is also developmentally controlled, we examined how early life seizures during the critical period of synaptogenesis could modify GluN development and function. In a postnatal day (P)10 rat model of neonatal seizures, we found that seizures could alter GluN2/3 subunit composition of GluNs and physiological function of synaptic GluNs. In hippocampal slices removed from rats within 48–96 h following seizures, the amplitudes of synaptic GluN-mediated evoked excitatory postsynaptic currents (eEPSCs) were elevated in CA1 pyramidal neurons. Moreover, GluN eEPSCs showed a decreased sensitivity to GluN2B selective antagonists and decreased Mg2+ sensitivity at negative holding potentials, indicating a higher proportion of GluN2A and GluN3A subunit function, respectively. These physiological findings were accompanied by a concurrent increase in GluN2A phosphorylation and GluN3A protein. These results suggest that altered GluN function and expression could potentially contribute to future epileptogenesis following neonatal seizures, and may represent potential therapeutic targets for the blockade of future epileptogenesis in the developing brain. PMID:26441533

Late-onset childhood neuronal ceroid lipofuscinosis: Early clinical and electroencephalographic markers.

PubMed

Beltrán, Lucas; Valenzuela, Gabriela Reyes; Loos, Mariana; Vargas, Rodrigo; Lizama, Rafael; Spinsanti, Pablo; Caraballo, Roberto

2018-05-15

The objective of the study was to describe the initial clinical and electroencephalographic findings in children with late-infantile neuronal ceroid lipofuscinosis (LINCL). The clinical charts of 35 patients seen between 1990 and 2016 were reviewed. The patients were divided into two groups: Group 1 (G1) consisting of 12 patients with NCL type 2 (CLN2) disease confirmed by enzymatic activity in dried blood spots on filter paper and/or genetic studies, and Group 2 (G2) consisting of 23 patients with a diagnosis of LINCL based on pathology studies by muscle biopsy. Mean age at symptom onset was 3 years in G1 and 3.4 years in G2. Symptoms at onset were epilepsy in 58%, language delay in 34%, and gait disturbances in 8% of patients in G1 and epilepsy in 52.1%, language delay in 26%, gait disturbances in 17.4%, and loss of visual acuity in 4.5% in G2. The most common seizure types in G1 patients were myoclonic in 3/7, generalized tonic-clonic in 2/7, focal motor in 1/7, and febrile seizures in 1/7; in G2 patients they were myoclonic in 5/12, generalized tonic-clonic in 3/12, myoclonic-atonic in 2/12, and febrile seizures in 2/12. A photoparoxysmal response to intermittent photic stimulation (IPS) was found in the initial EEG in 9/12 patients in G1 (mean age 3.8 years) and in 10/13 patients in G2 (mean age 3.9 years). There were no significant differences between both groups. Seizures, especially myoclonic, are the most common symptom at onset followed by language delay and gait disturbances. Low-frequency IPS is a useful study that may help facilitate the diagnosis of the disease. Copyright © 2018 Elsevier B.V. All rights reserved.

Child health and parental stress in school-age children with a preschool diagnosis of developmental delay.

PubMed

Webster, Richard I; Majnemer, Annette; Platt, Robert W; Shevell, Michael I

2008-01-01

Chronic disorders are known to have a wide-ranging impact on overall health and family dynamics. The objective of this study was to assess child health and well-being and parental stress in a cohort of school-age children diagnosed before school entry with either global developmental delay or developmental language impairment. In total, 65 children with preschool developmental delay were assessed at school age (mean +/- SD age: 7.3 +/- 0.7 years) with the Child Health Questionnaire and Parenting Stress Index, with a mean interval between assessment of 3.9 years. Almost all children who completed testing (60/62) continued to show developmental impairments across domains. On the Child Health Questionnaire, children showed the greatest impairment on the mental health scale (median z score: -0.9). The median Child Health Questionnaire psychosocial health score (40.7) was almost 1 SD below established normative values ( P < .001). More than 40% of parents had a Parenting Stress Index above the 85th percentile (clinically significant parenting stress). Using multiple linear regression analysis, high levels of parenting stress were best predicted by a child's Child Health Questionnaire psychosocial health score (r2 = 0.49, P < .001). Thus, 4 years after a preschool-age diagnosis of developmental delay, poor psychosocial health was a common comorbidity. Almost half the parents showed clinically significant levels of parenting stress. There is a need to both recognize and provide ongoing social and emotional support for young children diagnosed with developmental disability and their families.

The interaction between early life epilepsy and autistic-like behavioral consequences: a role for the mammalian target of rapamycin (mTOR) pathway.

PubMed

Talos, Delia M; Sun, Hongyu; Zhou, Xiangping; Fitzgerald, Erin C; Jackson, Michele C; Klein, Peter M; Lan, Victor J; Joseph, Annelise; Jensen, Frances E

2012-01-01

Early life seizures can result in chronic epilepsy, cognitive deficits and behavioral changes such as autism, and conversely epilepsy is common in autistic children. We hypothesized that during early brain development, seizures could alter regulators of synaptic development and underlie the interaction between epilepsy and autism. The mammalian Target of Rapamycin (mTOR) modulates protein translation and is dysregulated in Tuberous Sclerosis Complex, a disorder characterized by epilepsy and autism. We used a rodent model of acute hypoxia-induced neonatal seizures that results in long term increases in neuronal excitability, seizure susceptibility, and spontaneous seizures, to determine how seizures alter mTOR Complex 1 (mTORC1) signaling. We hypothesized that seizures occurring at a developmental stage coinciding with a critical period of synaptogenesis will activate mTORC1, contributing to epileptic networks and autistic-like behavior in later life. Here we show that in the rat, baseline mTORC1 activation peaks during the first three postnatal weeks, and induction of seizures at postnatal day 10 results in further transient activation of its downstream targets phospho-4E-BP1 (Thr37/46), phospho-p70S6K (Thr389) and phospho-S6 (Ser235/236), as well as rapid induction of activity-dependent upstream signaling molecules, including BDNF, phospho-Akt (Thr308) and phospho-ERK (Thr202/Tyr204). Furthermore, treatment with the mTORC1 inhibitor rapamycin immediately before and after seizures reversed early increases in glutamatergic neurotransmission and seizure susceptibility and attenuated later life epilepsy and autistic-like behavior. Together, these findings suggest that in the developing brain the mTORC1 signaling pathway is involved in epileptogenesis and altered social behavior, and that it may be a target for development of novel therapies that eliminate the progressive effects of neonatal seizures.

The Interaction between Early Life Epilepsy and Autistic-Like Behavioral Consequences: A Role for the Mammalian Target of Rapamycin (mTOR) Pathway

PubMed Central

Fitzgerald, Erin C.; Jackson, Michele C.; Klein, Peter M.; Lan, Victor J.; Joseph, Annelise; Jensen, Frances E.

2012-01-01

Early life seizures can result in chronic epilepsy, cognitive deficits and behavioral changes such as autism, and conversely epilepsy is common in autistic children. We hypothesized that during early brain development, seizures could alter regulators of synaptic development and underlie the interaction between epilepsy and autism. The mammalian Target of Rapamycin (mTOR) modulates protein translation and is dysregulated in Tuberous Sclerosis Complex, a disorder characterized by epilepsy and autism. We used a rodent model of acute hypoxia-induced neonatal seizures that results in long term increases in neuronal excitability, seizure susceptibility, and spontaneous seizures, to determine how seizures alter mTOR Complex 1 (mTORC1) signaling. We hypothesized that seizures occurring at a developmental stage coinciding with a critical period of synaptogenesis will activate mTORC1, contributing to epileptic networks and autistic-like behavior in later life. Here we show that in the rat, baseline mTORC1 activation peaks during the first three postnatal weeks, and induction of seizures at postnatal day 10 results in further transient activation of its downstream targets phospho-4E-BP1 (Thr37/46), phospho-p70S6K (Thr389) and phospho-S6 (Ser235/236), as well as rapid induction of activity-dependent upstream signaling molecules, including BDNF, phospho-Akt (Thr308) and phospho-ERK (Thr202/Tyr204). Furthermore, treatment with the mTORC1 inhibitor rapamycin immediately before and after seizures reversed early increases in glutamatergic neurotransmission and seizure susceptibility and attenuated later life epilepsy and autistic-like behavior. Together, these findings suggest that in the developing brain the mTORC1 signaling pathway is involved in epileptogenesis and altered social behavior, and that it may be a target for development of novel therapies that eliminate the progressive effects of neonatal seizures. PMID:22567115

Oral Health Characteristics and Dental Rehabilitation of Children with Global Developmental Delay.

PubMed

Kumar, Saurabh; Pai, Deepika; Saran, Runki

2017-01-01

Global developmental delay (GDD) is a chronic neurological disturbance which includes defects in one or more developmental domains. The developmental domain can be motor, cognitive, daily activities, speech or language, and social or personal development. The etiology for GDD can be prenatal, perinatal, or postnatal. It can be diagnosed early in childhood as the delay or absence of one or more developmental milestones. Hence the role of pedodontist and pediatricians becomes more crucial in identifying this condition. The diagnosis of GDD requires a detailed history including family history and environmental risk factors followed by physical and neurological examinations. Investigations for GDD include diagnostic laboratory tests, brain imaging, and other evidence-based evaluations. GDD affects multiple developmental domains that not only have direct bearing on maintenance of oral health, but also require additional behavior management techniques to deliver optimal dental care. This paper describes two different spectra of children with GDD. Since the severity of GDD can vary, this paper also discusses the different behavior management techniques that were applied to provide dental treatment in such children.

A novel ALDH5A1 mutation is associated with succinic semialdehyde dehydrogenase deficiency and severe intellectual disability in an Iranian family.

PubMed

Püttmann, Lucia; Stehr, Henning; Garshasbi, Masoud; Hu, Hao; Kahrizi, Kimia; Lipkowitz, Bettina; Jamali, Payman; Tzschach, Andreas; Najmabadi, Hossein; Ropers, Hans-Hilger; Musante, Luciana; Kuss, Andreas W

2013-08-01

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a disorder of the catabolism of the neurotransmitter gamma-aminobutyric acid (GABA) with a very variable clinical phenotype ranging from mild intellectual disability to severe neurological defects. We report here on a large Iranian family with four affected patients presenting with severe intellectual disability, developmental delay and generalized tonic-clonic seizures. Molecular genetic analysis revealed a missense mutation c.901A>G (p.K301E, RefSeq number NM_001080) in ALDH5A1 co-segregating with the disease in the family. The missense mutation affects an amino acid residue that is highly conserved across the animal kingdom. Protein modeling showed that p.K301E most likely leads to a loss of NAD(+) binding and a predicted decrease in the free energy by 6.67 kcal/mol furthermore suggests a severe destabilization of the protein. In line with these in silico observations, no SSADH enzyme activity could be detected in patient lymphoblasts. Copyright © 2013 Wiley Periodicals, Inc.

Monosomy1p36.3 and trisomy 19p13.3 in a child with periventricular nodular heterotopia.

PubMed

Descartes, Maria; Mikhail, Fady M; Franklin, Judith C; McGrath, Tony M; Bebin, Martina

2011-10-01

Monosomy 1p36 is a clinically recognizable syndrome that is considered to be the most common terminal deletion syndrome. It has characteristic clinical features that include craniofacial dysmorphism, congenital anomalies, hearing deficits, developmental delay, mental retardation, hypotonia, seizures, and brain anomalies. Brain anomalies in patients with 1p36 deletion are frequent but inconsistent. To date, 2 cases with monosomy 1p36 associated with periventricular nodular heterotopia (PNH) have been reported. We report a 2-month-old boy with multiple congenital anomalies; brain magnetic resonance imaging revealed PNH. The first 2 described cases were pure terminal deletions, whereas our patient carried unbalanced translocation due to an adjacent 1 segregation of a balanced maternal translocation, resulting in monosomy 1p36.3 and trisomy 19p13.3 identified by whole-genome array comparative genomic hybridization analysis. Our patient, with a smaller deletion that the 2 previously reported cases, can help narrow the critical region for PNH in association with the 1p36 deletion. Several potential candidate genes are discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

Models for discovery of targeted therapy in genetic epileptic encephalopathies.

PubMed

Maljevic, Snezana; Reid, Christopher A; Petrou, Steven

2017-10-01

Epileptic encephalopathies are severe disorders emerging in the first days to years of life that commonly include refractory seizures, various types of movement disorders, and different levels of developmental delay. In recent years, many de novo occurring variants have been identified in individuals with these devastating disorders. To unravel disease mechanisms, the functional impact of detected variants associated with epileptic encephalopathies is investigated in a range of cellular and animal models. This review addresses efforts to advance and use such models to identify specific molecular and cellular targets for the development of novel therapies. We focus on ion channels as the best-studied group of epilepsy genes. Given the clinical and genetic heterogeneity of epileptic encephalopathy disorders, experimental models that can reflect this complexity are critical for the development of disease mechanisms-based targeted therapy. The convergence of technological advances in gene sequencing, stem cell biology, genome editing, and high throughput functional screening together with massive unmet clinical needs provides unprecedented opportunities and imperatives for precision medicine in epileptic encephalopathies. © 2017 International Society for Neurochemistry.

Syndrome of microcephaly, Dandy-Walker malformation, and Wilms tumor caused by mosaic variegated aneuploidy with premature centromere division (PCD): report of a new case and review of the literature.

PubMed

Kawame, H; Sugio, Y; Fuyama, Y; Hayashi, Y; Suzuki, H; Kurosawa, K; Maekawa, K

1999-01-01

We report a male infant with multiple congenital anomalies and mosaic variegated aneuploidy; a rare cytogenetic abnormality characterized by mosaicism for several different aneuploidies involving many different chromosomes. He had prenatal-onset growth retardation, microcephaly, dysmorphic face, seizures, hypotonia, feeding difficulty, and developmental delay. In addition, he developed bilateral Wilms tumors. Neuroradiological examination revealed Dandy-Walker malformation and hypoplasia of the cerebral hemisphere and pons. Cytogenetic analysis revealed various multiple numerical aneuploidies in blood lymphocytes, fibroblasts, and bone marrow cells, together with premature centromere division (PCD). Peripheral blood chromosome analysis from his parents also showed PCD, but no aneuploid cells. The clinical phenotype and multiple aneuploidies of the patient may be a consequence of the homozygous PCD trait inherited from his parents. Comparison with previously reported cases of multiple aneuploidy suggests that mosaic variegated aneuploidy with PCD may be a clinically recognizable syndrome with major phenotypes being mental retardation, microcephaly, structural brain anomalies (including Dandy-Walker malformation), and possible cancer predisposition.

Typical and atypical phenotypes of PNPO deficiency with elevated CSF and plasma pyridoxamine on treatment.

PubMed

Ware, Tyson L; Earl, John; Salomons, Gajja S; Struys, Eduard A; Peters, Heidi L; Howell, Katherine B; Pitt, James J; Freeman, Jeremy L

2014-05-01

Pyridox(am)ine phosphate oxidase (PNPO) deficiency causes severe early infantile epileptic encephalopathy and has been characterized as responding to pyridoxal-5'-phosphate but not to pyridoxine. Two males with PNPO deficiency and novel PNPO mutations are reported and their clinical, metabolic, and video-electroencephalographic (EEG) findings described. The first child showed electro-clinical responses to pyridoxine and deterioration when pyridoxine was withheld. At last review, he has well-controlled epilepsy with pyridoxal-5'-phosphate monotherapy and an autism spectrum disorder. The second child had a perinatal middle cerebral artery infarct and a myoclonic encephalopathy. He failed to respond to pyridoxine but responded well to pyridoxal-5'-phosphate. At the age of 21 months he has global developmental delay and hemiparesis but is seizure-free with pyridoxal-5'-phosphate monotherapy. Plasma and cerebrospinal fluid pyridoxamine levels were increased in both children during treatment with pyridoxine or pyridoxal-5'-phosphate. These observations indicate that differential responses to pyridoxine and pyridoxal-5'-phosphate treatment cannot be relied upon to diagnose PNPO deficiency. © 2013 Mac Keith Press.

Infantile onset diabetes mellitus in developing countries - India

PubMed Central

Varadarajan, Poovazhagi

2016-01-01

Infantile onset diabetes mellitus (IODM) is an uncommon metabolic disorder in children. Infants with onset of diabetes mellitus (DM) at age less than one year are likely to have transient or permanent neonatal DM or rarely type 1 diabetes. Diabetes with onset below 6 mo is a heterogeneous disease caused by single gene mutations. Literature on IODM is scanty in India. Nearly 83% of IODM cases present with diabetic keto acidosis at the onset. Missed diagnosis was common in infants with diabetes (67%). Potassium channel mutation with sulphonylurea responsiveness is the common type in the non-syndromic IODM and Wolcott Rallison syndrome is the common type in syndromic diabetes. Developmental delay and seizures were the associated co-morbid states. Genetic diagnosis has made a phenomenal change in the management of IODM. Switching from subcutaneous insulin to oral hypoglycemic drugs is a major clinical breakthrough in the management of certain types of monogenic diabetes. Mortality in neonatal diabetes is 32.5% during follow-up from Indian studies. This article is a review of neonatal diabetes and available literature on IODM from India. PMID:27022444

Effects of the synthetic neurosteroid ganaxolone on seizure activity and behavioral deficits in an Angelman syndrome mouse model.

PubMed

Ciarlone, Stephanie L; Wang, Xinming; Rogawski, Michael A; Weeber, Edwin J

2017-04-01

Angelman syndrome (AS) is a rare neurogenetic disorder characterized by severe developmental delay, motor impairments, and epilepsy. GABAergic dysfunction is believed to contribute to many of the phenotypic deficits seen in AS. We hypothesized that restoration of inhibitory tone mediated by extrasynaptic GABA A receptors could provide therapeutic benefit. Here, we report that ganaxolone, a synthetic neurosteroid that acts as a positive allosteric modulator of synaptic and extrasynaptic GABA A receptors, was anxiolytic, anticonvulsant, and improved motor deficits in the Ube3a-deficient mouse model of AS when administered by implanted mini-pump for 3 days or 4 weeks. Treatment for 4 weeks also led to recovery of spatial working memory and hippocampal synaptic plasticity deficits. This study demonstrates that ganaxolone ameliorates many of the behavioral abnormalities in the adult AS mouse, and tolerance did not occur to the therapeutic effects of the drug. The results support clinical studies to investigate ganaxolone as a symptomatic treatment for AS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bilingual Children's Lexical Strategies in a Narrative Task

ERIC Educational Resources Information Center

Barbosa, Poliana; Nicoladis, Elena; Keith, Margaux

2017-01-01

We investigated how bilinguals choose words in a narrative task, contrasting the possibilities of a developmental delay vs. compensatory strategies. To characterize a developmental delay, we compared younger (three to five years) and older (seven to ten years) children's lexicalization of target words (Study 1). The younger children told shorter…

Emotion Discourse, Social Cognition, and Social Skills in Children with and without Developmental Delays

ERIC Educational Resources Information Center

Fenning, Rachel M.; Baker, Bruce L.; Juvonen, Jaana

2011-01-01

This study examined parent-child emotion discourse, children's independent social information processing, and social skills outcomes in 146 families of 8-year-olds with and without developmental delays. Children's emergent social-cognitive understanding (internal state understanding, perspective taking, and causal reasoning and problem solving)…

Parenting Children with Developmental Delays: The Role of Positive Beliefs

ERIC Educational Resources Information Center

Paczkowski, Emilie; Baker, Bruce L.

2008-01-01

Parents of children with developmental delays consistently report higher levels of child behavior problems and also parenting stress than parents of typically developing children. This study examined how mothers' positive beliefs influence the relation between children's behavior problems and mothers' parenting stress among families of children…

Social Routines and Language Play: Developing Communication Responses in Developmentally Delayed Blind Children.

ERIC Educational Resources Information Center

Rogow, Sally M.

1983-01-01

Social routines, which combined nursery rhymes with carefully planned action sequences, were used to help two young developmentally delayed, visually handicapped children acquire communicative responses. Midway through the 3-year project, one child responded to words for objects, people, and actions. (Author/SEW)

Sleep Patterns in Preschool-Age Children with Autism, Developmental Delay, and Typical Development

ERIC Educational Resources Information Center

Goodlin-Jones, Beth L.; Tang, Karen; Liu, Jingyi; Anders, Thomas F.

2008-01-01

The study investigates sleep disorders by assessing the quantity and quality of sleep in preschool children with autism and comparing them with developmental delay without autism, and typical development. The results prove that sleep patterns are different in preschool children across all three categories.

Identification of Early Risk Factors for Developmental Delay

ERIC Educational Resources Information Center

Delgado, Christine E. F.; Vagi, Sara J.; Scott, Keith G.

2007-01-01

Statewide birth certificate and preschool exceptionality records were integrated to identify risk factors for developmental delay (DD). Epidemiological methods were used to investigate both individual-level and population-level risk for DD associated with a number of child and maternal factors. Infants born with very low birth weight were at the…

Teaching Ecologically-Based Communication Skills to Persons Who Are Developmentally Delayed.

ERIC Educational Resources Information Center

Sousie, Susan P.

The paper offers a framework for the design, implementation, and evaluation of appropriate, effective communication instructional programs for persons who are severely developmentally delayed. The use of an ecological approach that incorporates the instruction of communication skills with that of activities of daily living (ADL) is emphasized.…

Loss-of-function variants in NFIA provide further support that NFIA is a critical gene in 1p32-p31 deletion syndrome: A four patient series.

PubMed

Revah-Politi, Anya; Ganapathi, Mythily; Bier, Louise; Cho, Megan T; Goldstein, David B; Hemati, Parisa; Iglesias, Alejandro; Juusola, Jane; Pappas, John; Petrovski, Slavé; Wilson, Ashley L; Aggarwal, Vimla S; Anyane-Yeboa, Kwame

2017-12-01

The association between 1p32-p31 contiguous gene deletions and a distinct phenotype that includes anomalies of the corpus callosum, ventriculomegaly, developmental delay, seizures, and dysmorphic features has been long recognized and described. Recently, the observation of overlapping phenotypes in patients with chromosome translocations that disrupt NFIA (Nuclear factor I/A), a gene within this deleted region, and NFIA intragenic deletions has led to the hypothesis that NFIA is a critical gene within this region. The wide application and increasing accessibility of whole exome sequencing (WES) has helped identify new cases to support this hypothesis. Here, we describe four patients with loss-of-function variants in the NFIA gene identified through WES. The clinical presentation of these patients significantly overlaps with the phenotype described in previously reported cases of 1p32-p31 deletion syndrome, NFIA gene disruptions and intragenic NFIA deletions. Our cohort includes a mother and daughter as well as an unrelated individual who share the same nonsense variant (c.205C>T, p.Arg69Ter; NM_001145512.1). We also report a patient with a frameshift NFIA variant (c.159_160dupCC, p.Gln54ProfsTer49). We have compared published cases of 1p32-p31 microdeletion syndrome, translocations resulting in NFIA gene disruption, intragenic deletions, and loss-of-function mutations (including our four patients) to reveal that abnormalities of the corpus callosum, ventriculomegaly/hydrocephalus, macrocephaly, Chiari I malformation, dysmorphic features, developmental delay, hypotonia, and urinary tract defects are common findings. The consistent overlap in clinical presentation provides further evidence of the critical role of NFIA haploinsufficiency in the development of the 1p32-p31 microdeletion syndrome phenotype. © 2017 Wiley Periodicals, Inc.

Etiologic yield of subspecialists' evaluation of young children with global developmental delay.

PubMed

Shevell, M I; Majnemer, A; Rosenbaum, P; Abrahamowicz, M

2000-05-01

To determine the etiologic yield of subspecialists' evaluation of young children with global developmental delay. In addition, variables that may predict finding an underlying etiology were also identified. All children <5 years of age, referred over an 18-month period to subspecialty services for initial evaluation of a suspected developmental delay, were prospectively enrolled. Diagnostic yield was ascertained after the completion of clinical assessments and laboratory investigations requested by the evaluating physician. Ninety-nine children (71 boys) were found to have global developmental delay; 96% had a mild or moderate delay documented. An etiologic diagnosis was determined in 44. Four diagnoses (cerebral dysgenesis, hypoxic-ischemic encephalopathy, toxin exposure, chromosomal abnormalities) accounted for 34 of 44 (77%) of the diagnoses made. The presence of co-existing autistic traits was associated with significantly decreased diagnostic yield (0/19 vs 44/80, P <.0001), whereas specific historical features (eg, family history, toxin exposure, and perinatal difficulty; 23/32 vs 21/67, P =.0002) and findings on physical examination (eg, dysmorphology, microcephaly, and focal motor findings; 35/48 vs 9/51, P <.0001) were significantly associated with identifying a diagnosis. Multiple logistic regression analysis identified antenatal toxin exposure, microcephaly, focal motor findings, and the absence of autistic traits as significant predictor variables for the identification of an etiology. An etiologic diagnosis is often possible in the young child with global developmental delay, particularly in the absence of autistic features. Etiologic yield is augmented by presence of specific findings on history or physical examination on initial assessment.

Twins and virtual twins: Do genetic (as well as experiential) factors affect developmental risks?

PubMed

Segal, Nancy L; Tan, Tony Xing; Graham, Jamie L

2015-08-01

Factors underlying developmental delays and psychosocial risks are of interest to international adoption communities. The current study administered a Pre-Adoption Adversity (PAA) Questionnaire to mostly American parents raising (a) adopted Chinese twins or (b) same-age unrelated adopted siblings. A goal was to replicate earlier analyses of pre-adoption adversity/adjustment among adopted preschool-age Chinese girls. A second goal was to conduct genetic analyses of four content areas (Developmental Delays at Adoption, Initial Adaptation to Adoption, Crying/Clinging, and Refusal/Avoidance) derived from the PAA Questionnaire. A key finding was that age at adoption added less than other predictors to adoptees' externalizing and internalizing behaviors. Family factors (e.g., parental education) contributed significantly to behavioral outcomes among the adopted Chinese twins. Genetic effects were indicated for all four content areas, with shared environmental effects evident for Developmental Delays at Adoption and Crying/Clinging. Future investigators should consider incorporating genetically sensitive designs into developmental research programs. Copyright © 2015 Elsevier Inc. All rights reserved.

Electroencephalograms in epilepsy: analysis and seizure prediction within the framework of Lyapunov theory

NASA Astrophysics Data System (ADS)

Moser, H. R.; Weber, B.; Wieser, H. G.; Meier, P. F.

1999-06-01

Epileptic seizures are defined as the clinical manifestation of excessive and hypersynchronous activity of neurons in the cerebral cortex and represent one of the most frequent malfunctions of the human central nervous system. Therefore, the search for precursors and predictors of a seizure is of utmost clinical relevance and may even guide us to a deeper understanding of the seizure generating mechanisms. We extract chaos-indicators such as Lyapunov exponents and Kolmogorov entropies from different types of electroencephalograms (EEGs): this covers mainly intracranial EEGs (semi-invasive and invasive recording techniques), but also scalp-EEGs from the surface of the skin. Among the analytical methods we tested up to now, we find that the spectral density of the local expansion exponents is best suited to predict the onset of a forthcoming seizure. We also evaluate the time-evolution of the dissipation in these signals: it exhibits strongly significant variations that clearly relate to the time relative to a seizure onset. This article is mainly devoted to an assessment of these methods with respect to their sensitivity to EEG changes, e.g., prior to a seizure. Further, we investigate interictal EEGs (i.e., far away from a seizure) in order to characterize their more general properties, such as the convergence of the reconstructed quantities with respect to the number of phase space dimensions. Generally we use multichannel reconstruction, but we also present a comparison with the delay-embedding technique.

Dynamic timecourse of typical childhood absence seizures: EEG, behavior and fMRI

PubMed Central

Bai, X; Vestal, M; Berman, R; Negishi, M; Spann, M; Vega, C; Desalvo, M; Novotny, EJ; Constable, RT; Blumenfeld, H

2010-01-01

Absence seizures are 5–10 second episodes of impaired consciousness accompanied by 3–4Hz generalized spike-and-wave discharge on electroencephalography (EEG). The timecourse of functional magnetic resonance imaging (fMRI) changes in absence seizures in relation to EEG and behavior is not known. We acquired simultaneous EEG-fMRI in 88 typical childhood absence seizures from 9 pediatric patients. We investigated behavior concurrently using a continuous performance task (CPT) or simpler repetitive tapping task (RTT). EEG time-frequency analysis revealed abrupt onset and end of 3–4 Hz spike-wave discharges with a mean duration of 6.6 s. Behavioral analysis also showed rapid onset and end of deficits associated with electrographic seizure start and end. In contrast, we observed small early fMRI increases in the orbital/medial frontal and medial/lateral parietal cortex >5s before seizure onset, followed by profound fMRI decreases continuing >20s after seizure end. This timecourse differed markedly from the hemodynamic response function (HRF) model used in conventional fMRI analysis, consisting of large increases beginning after electrical event onset, followed by small fMRI decreases. Other regions, such as the lateral frontal cortex, showed more balanced fMRI increases followed by approximately equal decreases. The thalamus showed delayed increases after seizure onset followed by small decreases, most closely resembling the HRF model. These findings reveal a complex and long lasting sequence of fMRI changes in absence seizures, which are not detectible by conventional HRF modeling in many regions. These results may be important mechanistically for seizure initiation and termination and may also contribute to changes in EEG and behavior. PMID:20427649

Evidence-based guideline: Management of an unprovoked first seizure in adults: Report of the Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

PubMed

Krumholz, Allan; Wiebe, Samuel; Gronseth, Gary S; Gloss, David S; Sanchez, Ana M; Kabir, Arif A; Liferidge, Aisha T; Martello, Justin P; Kanner, Andres M; Shinnar, Shlomo; Hopp, Jennifer L; French, Jacqueline A

2015-04-21

To provide evidence-based recommendations for treatment of adults with an unprovoked first seizure. We defined relevant questions and systematically reviewed published studies according to the American Academy of Neurology's classification of evidence criteria; we based recommendations on evidence level. Adults with an unprovoked first seizure should be informed that their seizure recurrence risk is greatest early within the first 2 years (21%-45%) (Level A), and clinical variables associated with increased risk may include a prior brain insult (Level A), an EEG with epileptiform abnormalities (Level A), a significant brain-imaging abnormality (Level B), and a nocturnal seizure (Level B). Immediate antiepileptic drug (AED) therapy, as compared with delay of treatment pending a second seizure, is likely to reduce recurrence risk within the first 2 years (Level B) but may not improve quality of life (Level C). Over a longer term (>3 years), immediate AED treatment is unlikely to improve prognosis as measured by sustained seizure remission (Level B). Patients should be advised that risk of AED adverse events (AEs) may range from 7% to 31% (Level B) and that these AEs are likely predominantly mild and reversible. Clinicians' recommendations whether to initiate immediate AED treatment after a first seizure should be based on individualized assessments that weigh the risk of recurrence against the AEs of AED therapy, consider educated patient preferences, and advise that immediate treatment will not improve the long-term prognosis for seizure remission but will reduce seizure risk over the subsequent 2 years. © 2015 American Academy of Neurology.

Multimodal data and machine learning for surgery outcome prediction in complicated cases of mesial temporal lobe epilepsy.

PubMed

Memarian, Negar; Kim, Sally; Dewar, Sandra; Engel, Jerome; Staba, Richard J

2015-09-01

This study sought to predict postsurgical seizure freedom from pre-operative diagnostic test results and clinical information using a rapid automated approach, based on supervised learning methods in patients with drug-resistant focal seizures suspected to begin in temporal lobe. We applied machine learning, specifically a combination of mutual information-based feature selection and supervised learning classifiers on multimodal data, to predict surgery outcome retrospectively in 20 presurgical patients (13 female; mean age±SD, in years 33±9.7 for females, and 35.3±9.4 for males) who were diagnosed with mesial temporal lobe epilepsy (MTLE) and subsequently underwent standard anteromesial temporal lobectomy. The main advantage of the present work over previous studies is the inclusion of the extent of ipsilateral neocortical gray matter atrophy and spatiotemporal properties of depth electrode-recorded seizures as training features for individual patient surgery planning. A maximum relevance minimum redundancy (mRMR) feature selector identified the following features as the most informative predictors of postsurgical seizure freedom in this study's sample of patients: family history of epilepsy, ictal EEG onset pattern (positive correlation with seizure freedom), MRI-based gray matter thickness reduction in the hemisphere ipsilateral to seizure onset, proportion of seizures that first appeared in ipsilateral amygdala to total seizures, age, epilepsy duration, delay in the spread of ipsilateral ictal discharges from site of onset, gender, and number of electrode contacts at seizure onset (negative correlation with seizure freedom). Using these features in combination with a least square support vector machine (LS-SVM) classifier compared to other commonly used classifiers resulted in very high surgical outcome prediction accuracy (95%). Supervised machine learning using multimodal compared to unimodal data accurately predicted postsurgical outcome in patients with atypical MTLE. Published by Elsevier Ltd.

North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2

ClinicalTrials.gov

2018-06-06

Epilepsy; Seizure; Neuromuscular Diseases; Brain Malformation; Intellectual Disability; Autism Spectrum Disorder; Hypotonia; Inborn Errors of Metabolism; Movement Disorders; Genetic Disease; Development Delay; Chromosome Abnormality; Hearing Loss; Dysmorphic Features; Skeletal Dysplasia; Congenital Abnormality; Microcephaly; Macrocephaly

Phenotype and management of Aicardi syndrome: new findings from a survey of 69 children

USDA-ARS?s Scientific Manuscript database

Aicardi syndrome is a rare neurodevelopmental disorder characterized by agenesis of the corpus callosum, other developmental brain abnormalities, chorioretinal lacunae, and severe seizures. Current clinical knowledge is derived from small series that focus on these major defects. The authors perform...

Language screening in preschool Chinese children.

PubMed

Wong, V; Lee, P W; Lieh-Mak, F; Yeung, C Y; Leung, P W; Luk, S L; Yiu, E

1992-01-01

The incidence of language delay in Chinese preschool children was studied by a stratified proportional sampling of all 3 year olds in Hong Kong. The Developmental Language Screening Scale (DLSS) devised for use with Cantonese speaking children was used to identify children with language delay. Of 855 children sampled in the stage I screening procedure, 4%, 2.8% and 3.3% were identified as having delay in verbal comprehension, expression or both respectively. The stage II clinical diagnostic study included a randomly selected group of children screened in stage I with or without any associated behavioural problem. Among these, 3.4% were identified as having a language delay using the Reynell Language Developmental Scale (RDLS) with a criterion of language age of less than or equal to two-thirds of the chronological age; 3% had specific language delay using the criteria of language age less than or equal to two-thirds the chronological age and developmental age more than or equal to two-thirds the chronological age. More boys were found to have language delay, although this was not statistically significant.

Evaluation of levetiracetam effects on pilocarpine-induced seizures: cholinergic muscarinic system involvement.

PubMed

Oliveira, A A; Nogueira, C R A; Nascimento, V S; Aguiar, L M V; Freitas, R M; Sousa, F C F; Viana, G S B; Fonteles, M M F

2005-09-16

Levetiracetam (LEV) is a new antiepileptic drug effective as adjunctive therapy for partial seizures. It displays a unique pharmacological profile against experimental models of seizures, including pilocarpine-induced seizures in rodents. Aiming to clarify if anticonvulsant activity of LEV occurs due to cholinergic alterations, adult male mice received LEV injections before cholinergic agonists' administration. Pretreatment with LEV (30-200 mg/kg, i.p.) increased the latencies of seizures, but decreased status epilepticus and death on the seizure model induced by pilocarpine, 400 mg/kg, s.c. (P400). LEV (LEV200, 200 mg/kg, i.p.) pretreatment also reduced the intensity of tremors induced by oxotremorine (0.5 mg/kg, i.p). [3H]-N-methylscopolamine-binding assays in mice hippocampus showed that LEV200 pretreatment reverts the downregulation on muscarinic acetylcholine receptors (mAChR), induced by P400 administration, bringing back these density values to control ones (0.9% NaCl, i.p.). However, subtype-specific-binding assays revealed that P400- and LEV-alone treatments result in M1 and M2 subtypes decrease, respectively. The agonist-like behavior of LEV on the inhibitory M2 mAChR subtype, observed in this work, could contribute to explain the reduction on oxotremorine-induced tremors and the delay on pilocarpine-induced seizures, by an increase in the attenuation of neuronal activity mediated by the M1 receptors.

Low Frequency Stimulation Decreases Seizure Activity in a Mutation Model of Epilepsy

PubMed Central

Kile, Kara Buehrer; Tian, Nan; Durand, Dominique M.

2013-01-01

Summary Purpose To investigate brain electrical activity in Q54 mice that display spontaneous seizures because of a gain-of-function mutation of the Scn2a sodium channel gene, and to evaluate the efficacy of low frequency deep brain stimulation (DBS) for seizure frequency reduction. Methods EEG, EMG, and hippocampal deep electrodes were implanted into Q54 mice expressing an epileptic phenotype (n = 6). Chronic six channel recordings (wideband, 0.1–300 Hz) were stored 24 hours a day for more than 12 days. Low Frequency stimulation (LFS) (3Hz, square wave, biphasic, 100μs, 400μA) was applied to the ventral hippocampal commisure (VHC) in alternating five minute cycles (on or off) 24 hours a day for a period of four days. Results LFS (3Hz) resulted in a significant reduction in seizure frequency and duration (21% and 35%, p<0.05), when applied to the VHC of epileptic Q54 mice (n = 6). Seizure frequency was not directly affected by stimulation state (“on” versus “off”). Conclusion LFS applied at a frequency of 3Hz significantly reduced seizure frequency and duration in the Q54 model. Furthermore, the reduction of seizure frequency and duration by LFS was not immediate but had a delayed and lasting effect, supporting complex, indirect mechanisms of action. PMID:20659150

De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features.

PubMed

Tanaka, Akemi J; Cho, Megan T; Retterer, Kyle; Jones, Julie R; Nowak, Catherine; Douglas, Jessica; Jiang, Yong-Hui; McConkie-Rosell, Allyn; Schaefer, G Bradley; Kaylor, Julie; Rahman, Omar A; Telegrafi, Aida; Friedman, Bethany; Douglas, Ganka; Monaghan, Kristin G; Chung, Wendy K

2016-01-01

We identified five unrelated individuals with significant global developmental delay and intellectual disability (ID), dysmorphic facial features and frequent microcephaly, and de novo predicted loss-of-function variants in chromosome alignment maintaining phosphoprotein 1 (CHAMP1). Our findings are consistent with recently reported de novo mutations in CHAMP1 in five other individuals with similar features. CHAMP1 is a zinc finger protein involved in kinetochore-microtubule attachment and is required for regulating the proper alignment of chromosomes during metaphase in mitosis. Mutations in CHAMP1 may affect cell division and hence brain development and function, resulting in developmental delay and ID.

Effects of overweight and obesity on motor and mental development in infants and toddlers.

PubMed

Cataldo, R; Huang, J; Calixte, R; Wong, A T; Bianchi-Hayes, J; Pati, S

2016-10-01

A consequence of childhood obesity may be poor developmental outcomes. This study aimed to examine the relationship between weight and developmental delays in young children. We conducted a secondary analysis of the Early Childhood Longitudinal Study Birth Cohort data. Logistic regression models quantified the association between different weight statuses (normal weight <85th, overweight ≥90th, obese ≥95th percentile for weight) and delays in motor and mental development. Children classified as overweight in both waves had higher percentages of delays in wave 2 (motor [7.5 vs. 6.2-6.4%], mental [8.6 vs. 5.9-6.7%]), as well as wave 1 and/or wave 2 (motor [14.8 vs. 10.9-13.0%], mental [11.9 vs. 9.0-10.1%]), compared with other children. This association was also found in children who were obese at both time points in wave 2 (motor delay [8.9 vs. 4.9-7.3%], mental delay [10.3 vs. 6.0-7.2%]), as well as wave 1 and/or wave 2 (motor delay [14.5 vs. 10.9-12.9%], mental delay [14.1 vs. 9.4-10.1%]). In the adjusted models, children classified as always obese were more likely to have a mental delay in wave 2 (adjusted odds ratio [aOR] 1.89, 95% confidence interval [CI]: 1.21-2.95) as well as wave 1 and/or wave 2 (aOR 1.56, 95% CI: 1.08-2.26). These children were also more likely to have motor delay (aOR 1.47, 95% CI: 1.02-2.13) in wave 1 and/or wave 2. Overweight children are more likely than their normal-weight peers to have motor and mental developmental delays. Preventing obesity during infancy may facilitate reducing developmental delays in young children. © 2015 World Obesity.

Scalp defects, polythelia, microcephaly, and developmental delay: a new syndrome with apparent autosomal dominant inheritance.

PubMed

Marble, Michael; Pridjian, Gabriella

2002-04-01

We report a family with apparent autosomal dominant inheritance of scalp defects, polythelia, microcephaly, and developmental delay. A review of the literature revealed no previous report of this combination of anomalies. We conclude that these patients have a new autosomal dominant syndrome. Copyright 2002 Wiley-Liss, Inc.

Maternal Immune-Mediated Conditions, Autism Spectrum Disorders, and Developmental Delay

ERIC Educational Resources Information Center

Lyall, Kristen; Ashwood, Paul; Van de Water, Judy; Hertz-Picciotto, Irva

2014-01-01

The maternal immune system may play a role in offspring neurodevelopment. We examined whether maternal autoimmune disease, asthma, and allergy were associated with child autism spectrum disorder (ASD) and developmental delay without autism (DD) using 560 ASD cases, 391 typically developing controls, and 168 DD cases from the CHildhood Autism Risk…

Predicting Declassification of Preschool Disabled Students through a Combination of Variables

ERIC Educational Resources Information Center

DeFina, Cynthia E.

2017-01-01

Early learning programs impact students, especially those with developmental delays. These formative years play a vital role in the overall development of the students' skills. School districts want to reach these special education students during these crucial years to help close the developmental delay gap. This quantitative study examines the…

Graduated Guidance Delivered by Parents to Teach Yoga to Children with Developmental Delays

ERIC Educational Resources Information Center

Gruber, Deborah J.; Poulson, Claire L.

2016-01-01

We evaluated the effects of a parent-implemented intervention to teach yoga poses to 3 children with developmental delays. Graduated guidance, provided by the participants' mothers, was introduced in a multiple baseline design across the participants. With the introduction of intervention, imitation of the response chains increased over baseline…

Marital Satisfaction, Parental Stress, and Child Behavior Problems among Parents of Young Children with Developmental Delays

ERIC Educational Resources Information Center

Robinson, Merideth; Neece, Cameron L.

2015-01-01

Studies have found that low marital satisfaction, parenting stress, and child behavior problems are linked in families of children with developmental delays (DD). However, previous investigations examining the relationships between parenting stress, child behavior problems, and marital satisfaction rarely examine the interrelationships of these…

Paternal versus Maternal Coping Styles with Child Diagnosis of Developmental Delay

ERIC Educational Resources Information Center

Barak-Levy, Yael; Atzaba-Poria, Na'ama

2013-01-01

Parents of children with disabilities vary in their reaction to their children's diagnosis. The current study focused on fathers in addition to mothers and examined their resolution and coping styles when having children diagnosed with developmental delay (DD). Sixty-five fathers and 71 mothers were interviewed using the reaction to the diagnosis…

A Classroom Collaborative Strategy Designed To Improve Oral Motor Skill Deficits in Developmentally Delayed Pre-Kindergarten Students.

ERIC Educational Resources Information Center

Hoffman, Lorri J.

This practicum report describes the design and implementation of an oral motor program to increase the verbal communication skills of seven pre-kindergarten children with developmental delays, including hypotonia in oral motor development with moderate to severe articulation difficulties. Collaborative planning by the pre-kindergarten special…

Preschool Children with and without Developmental Delay: Risk, Parenting, and Child Demandingness

ERIC Educational Resources Information Center

Brown, Mallory A.; McIntyre, Laura Lee; Crnic, Keith A.; Baker, Bruce L.; Blacher, Jan

2011-01-01

Although past literature has established relations between early child risk factors, negative parenting, and problematic child behavior, the nature of these interrelations and pathways of influence over time remains largely unknown, especially in children with developmental delays or disabilities. In the current study, data were drawn from the…

Perceptions of Early Intervention Services: Adolescent and Adult Mothers in Two States

ERIC Educational Resources Information Center

Thompson, Stacy D.; Bruns, Deborah A.

2013-01-01

Early intervention (EI) provides critical services to families with young children who have diagnosed disabilities, developmental delays, or who are at-risk for developmental delays. Very little is known about the experiences of adolescent mothers who have children who qualify for EI services. The authors investigated the perceptions of adolescent…

Hyperresponsive Sensory Patterns in Young Children with Autism, Developmental Delay, and Typical Development

ERIC Educational Resources Information Center

Baranek, Grace T.; Boyd, Brian A.; Poe, Michele D.; David, Fabian J.; Watson, Linda R.

2007-01-01

The nature of hyperresponsiveness to sensory stimuli in children with autism, using a new observational measure, the SPA, was examined. Three groups of young participants were assessed (autism, developmental delay, typical). Across all groups, MA was a predictor of hyperresponsiveness, such that aversion to multisensory toys decreased as MA…

Establishing Auditory-Tactile-Visual Equivalence Classes in Children with Autism and Developmental Delays

ERIC Educational Resources Information Center

Mullen, Stuart; Dixon, Mark R.; Belisle, Jordan; Stanley, Caleb

2017-01-01

The current study sought to evaluate the efficacy of a stimulus equivalence training procedure in establishing auditory-tactile-visual stimulus classes with 2 children with autism and developmental delays. Participants were exposed to vocal-tactile (A-B) and tactile-picture (B-C) conditional discrimination training and were tested for the…

The Negative Effects of Positive Reinforcement in Teaching Children with Developmental Delay.

ERIC Educational Resources Information Center

Biederman, Gerald B.; And Others

1994-01-01

This study compared the performance of 12 children (ages 4 to 10) with developmental delay, each trained in 2 tasks, one through interactive modeling (with or without verbal reinforcement) and the other through passive modeling. Results showed that passive modeling produced better rated performance than interactive modeling and that verbal…

Gastrointestinal Problems in Children with Autism, Developmental Delays or Typical Development

ERIC Educational Resources Information Center

Chaidez, Virginia; Hansen, Robin L.; Hertz-Picciotto, Irva

2014-01-01

To compare gastrointestinal (GI) problems among children with: (1) autism spectrum disorder (ASD), (2) developmental delay (DD) and (3) typical development (TD), GI symptom frequencies were obtained for 960 children from the CHildhood Autism Risks from Genetics and Environment (CHARGE) study. We also examined scores on five Aberrant Behavior…

Movement Exploration as a Technique for Teaching Pre-Swimming Skills to Students with Developmental Delays.

ERIC Educational Resources Information Center

Buis, Joyce M.; Schane, Catherine S.

1980-01-01

Background, rationale, and techniques for using movement exploration to teach preswimming skills to developmentally delayed persons are given. Objectives (beyond the primary one of safety) of such a program include body awareness, spatial awareness, movement, and perceptual motor functions. Guidelins for activity selection and adaptation are…

Requirement of longitudinal synchrony of epileptiform discharges in the hippocampus for seizure generation: a pilot study.

PubMed

Umeoka, Shuichi C; Lüders, Hans O; Turnbull, John P; Koubeissi, Mohamad Z; Maciunas, Robert J

2012-03-01

The goal in this study was to assess the role of longitudinal hippocampal circuits in the generation of interictal and ictal activity in temporal lobe epilepsy (TLE) and to evaluate the effects of multiple hippocampal transections (MHT). In 6 patients with TLE, the authors evaluated the synchrony of hippocampal interictal and ictal epileptiform discharges by using a cross-correlation analysis, and the effect of MHT on hippocampal interictal spikes was studied. Five of the 6 patients were studied with depth electrodes, and epilepsy surgery was performed in 4 patients (anterior temporal lobectomy in 1 and MHT in 3). Four hundred eighty-two (95.1%) of 507 hippocampal spikes showed an anterior-to-posterior propagation within the hippocampus, with a fixed peak-to-peak interval. During seizures, a significant increase of synchronization between different hippocampal regions and between the hippocampus and the ipsilateral anterior parahippocampal gyrus was observed in all seizures. An ictal increase in synchronization between the hippocampus and ipsilateral amygdala was seen in only 24.1% of the seizures. No changes in synchronization were noticed during seizures between the hippocampi and the amygdala on either side. The structure leading the epileptic seizures varied over time during a given seizure and also from one seizure to another. Spike analysis during MHT demonstrated that there were two spike populations that reacted differently to this procedure--namely, 1) spikes that showed maximum amplitude at the head of the hippocampus (type H); and 2) spikes that showed the highest amplitude at the hippocampal body (type B). A striking decrease in amplitude and frequency of type B spikes was noticed in all 3 patients after transections at the head or anterior portion of the hippocampal body. Type H spikes were seen in 2 cases and did not change in amplitude and frequency throughout MHT. Type B spikes showed constantly high cross-correlation values in different derivations and a relatively fixed peak-to-peak interval before MHT. This fixed interpeak delay disappeared after the first transection, although high cross-correlation values persisted unchanged. All patients who underwent MHT remained seizure free for more than 2 years. These data suggest that synchronized discharges involving the complete anterior-posterior axis of the hippocampal/parahippocampal (H/P) formation underlie the spread of epileptiform discharges outside the H/P structures and, therefore, for the generation of epileptic seizures originating in the H/P structures. This conclusion is supported by the following observations. 1) Hippocampal spikes are consistently synchronized in the whole hippocampal structures, with a fixed delay between the different hippocampal areas. 2) One or two transections between the head and body of the hippocampal formation are sufficient to abolish hippocampal spikes that are synchronized along the anterior-posterior axis of the hippocampus. 3) Treatment with MHT leads to seizure freedom in patients with H/P epilepsy.

Mathematical problems in children with developmental coordination disorder.

PubMed

Pieters, Stefanie; Desoete, Annemie; Van Waelvelde, Hilde; Vanderswalmen, Ruth; Roeyers, Herbert

2012-01-01

Developmental coordination disorder (DCD) is a heterogeneous disorder, which is often co-morbid with learning disabilities. However, mathematical problems have rarely been studied in DCD. The aim of this study was to investigate the mathematical problems in children with various degrees of motor problems. Specifically, this study explored if the development of mathematical skills in children with DCD is delayed or deficient. Children with DCD performed significantly worse for number fact retrieval and procedural calculation in comparison with age-matched control children. Moreover, children with mild DCD differed significantly from children with severe DCD on both number fact retrieval and procedural calculation. In addition, we found a developmental delay of 1 year for number fact retrieval in children with mild DCD and a developmental delay of 2 years in children with severe DCD. No evidence for a mathematical deficit was found. Diagnostic implications are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

The effectiveness of parent participation in occupational therapy for children with developmental delay

PubMed Central

Lin, Chien-Lin; Lin, Chin-Kai; Yu, Jia-Jhen

2018-01-01

Introduction This study aims to explore the impact of Parent Participation Program on the development of developmental delay children. Methods Pretest-posttest equivalent-group experimental design study was used in this paper. A total of 30 pairs of developmental delay children aged 0–72 months and their parents participated into this study. They were divided into two groups, namely control group and experimental group, according to parents’ wishes. The objects of study in control group received 16 courses of direct rehabilitation therapy; those in experimental group received 8 courses of direct rehabilitation therapy and 8 courses of instruction and tracking of Parent Participation Program. The duration of the intervention was 8 weeks. All cases should be evaluated before and after the intervention, to analyze the difference before and after intervention and among groups. The statistical methods in this paper included descriptive analysis, Chi-square test, independent sample t-test, pair-sample t-test. Results and conclusion The intervention of Parent Participation Occupational Program has positive impact on the development of developmental delay children in various fields. Among all the intervention results, the progress of the experimental group is 1.895 times more than that of the control group. With parent involvement, Parent Participation Occupational Therapy can promote the cognitive ability, language ability, action ability (gross and fine movement), social competence and self-care ability of children with developmental delay. Finally, the researcher presents suggestions and directions for future research in accordance with the results. PMID:29503546

Factors affecting the causality assessment of adverse events following immunisation in paediatric clinical trials: An online survey.

PubMed

Voysey, Merryn; Tavana, Rahele; Farooq, Yama; Heath, Paul T; Bonhoeffer, Jan; Snape, Matthew D

2015-12-16

Serious adverse events (SAEs) in clinical trials require reporting within 24h, including a judgment of whether the SAE was related to the investigational product(s). Such assessments are an important component of pharmacovigilance, however classification systems for assigning relatedness vary across study protocols. This on-line survey evaluated the consistency of SAE causality assessment among professionals with vaccine clinical trial experience. Members of the clinical advisory forum of experts (CAFÉ), a Brighton Collaboration online-forum, were emailed a survey containing SAEs from hypothetical vaccine trials which they were asked to classify. Participants were randomised to either two classification options (related/not related to study immunisation) or three options (possibly/probably/unrelated). The clinical scenarios, were (i) leukaemia diagnosed 5 months post-immunisation with a live RSV vaccine, (ii) juvenile idiopathic arthritis (JIA) 3 months post-immunisation with a group A streptococcal vaccine, (iii) developmental delay diagnosed at age 10 months after infant capsular group B meningococcal vaccine, (iv) developmental delay diagnosed at age 10 months after maternal immunisation with a group B streptococcal vaccine. There were 140 respondents (72 two options, 68 three options). Across all respondents, SAEs were considered related to study immunisation by 28% (leukaemia), 74% (JIA), 29% (developmental delay after infant immunisation) and 42% (developmental delay after maternal immunisation). Having only two options made respondents significantly less likely to classify the SAE as immunisation-related for two scenarios (JIA p=0.0075; and maternal immunisation p=0.045). Amongst study investigators (n=43) this phenomenon was observed for three of the four scenarios: (JIA p=0.0236; developmental delay following infant immunisation p=0.0266; and developmental delay after maternal immunisation p=0.0495). SAE causality assessment is inconsistent amongst study investigators and can be influenced by the classification systems available to them. There is a pressing need for SAE classification systems to be standardised across study protocols. Copyright © 2015 Elsevier Ltd. All rights reserved.

Childhood absence epilepsy successfully treated with the paleolithic ketogenic diet.

PubMed

Clemens, Zsófia; Kelemen, Anna; Fogarasi, András; Tóth, Csaba

2013-12-01

Childhood absence epilepsy is an epilepsy syndrome responding relatively well to the ketogenic diet with one-third of patients becoming seizure-free. Less restrictive variants of the classical ketogenic diet, however, have been shown to confer similar benefits. Beneficial effects of high fat, low-carbohydrate diets are often explained in evolutionary terms. However, the paleolithic diet itself which advocates a return to the human evolutionary diet has not yet been studied in epilepsy. Here, we present a case of a 7-year-old child with absence epilepsy successfully treated with the paleolithic ketogenic diet alone. In addition to seizure freedom achieved within 6 weeks, developmental and behavioral improvements were noted. The child remained seizure-free when subsequently shifted toward a paleolithic diet. It is concluded that the paleolithic ketogenic diet was effective, safe and feasible in the treatment of this case of childhood absence epilepsy.

Megalencephalic Leukoencephalopathy with Subcortical Cysts (MLC)

MedlinePlus

... patients, the first symptom is an increase in head circumference in the first year of life. Patients can have a delayed development and may subsequently show neurological deterioration ... an abnormally large head Seizures (present in ~75% of patients and most ...

Infective Causes of Epilepsy.

PubMed

Bonello, M; Michael, B D; Solomon, T

2015-06-01

A wide range of infections of the central nervous system are responsible for both acute seizures and epilepsy. The pathogenesis and clinical semiology of the seizure disorders vary widely between the infective pathogens. The exact mechanisms underlying this are poorly understood, but appear, at least in part, to relate to the pathogen; the degree of cortical involvement; delays in treatment; and the host inflammatory response. The treatment of infective causes of seizures involves both symptomatic treatment with antiepileptic drugs and direct treatment of the underlying condition. In many cases, early treatment of the infection may affect the prognosis of the epilepsy syndrome. The greatest burden of acute and long-term infection-related seizures occurs in resource-poor settings, where both clinical and research facilities are often lacking to manage such patients adequately. Nevertheless, education programs may go a long way toward addressing the stigma, leading to improved diagnosis, management, and ultimately to better quality of life. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Individual development of preschool children-prevalences and determinants of delays in Germany: a cross-sectional study in Southern Bavaria.

PubMed

Stich, Heribert L; Baune, Bernhard Th; Caniato, Riccardo N; Mikolajczyk, Rafael T; Krämer, Alexander

2012-12-05

Even minor abnormalities of early child development may have dramatic long term consequences. Accurate prevalence rates for a range of developmental impairments have been difficult to establish. Since related studies have used different methodological approaches, direct comparisons of the prevalence of developmental delays are difficult. The understanding of the key factors affecting child development, especially in preschool aged children remains limited. We used data from school entry examinations in Bavaria to measure the prevalence of developmental impairments in pre-school children beginning primary school in 1997-2009. The developmental impairments of all school beginners in the district of Dingolfing-Landau, Bavaria were assessed using modified "Bavarian School Entry Model" examination from 1997 to 2009 (N=13,182). The children were assessed for motor, cognitive, language and psychosocial impairments using a standardised medical protocol. Prevalence rates of impairments in twelve domains of development were estimated. Using uni- and multivariable logistic regression models, association between selected factors and development delays were assessed. The highest prevalence existed for impairments of pronunciation (13.8%) followed by fine motor impairments (12.2%), and impairments of memory and concentration (11.3%) and the lowest for impairments of rhythm of speech (3.1%). Younger children displayed more developmental delays. Male gender was strongly associated with all developmental impairments (highest risk for fine motor impairments = OR 3.22, 95% confidence interval 2.86-3.63). Preschool children with siblings (vs. children without any siblings) were at higher risk of having impairments in pronunciation (OR 1.31, 1.14-1.50). The influence of the non-German nationality was strong, with a maximum risk increase for the subareas of grammar and psychosocial development. Although children with non-German nationality had a reduced risk of disorders for the rhythm of speech and pronunciation, in all other 10 subareas their risk was increased. In preschool children, most common were delays of pronunciation, memory and concentration. Age effects suggest that delays can spontaneously resolve, but providing support at school entry might be helpful. Boys and migrant children appear at high risk of developmental problems, which may warrant tailored intervention strategies.

Alterations in Sociability and Functional Brain Connectivity Caused by Early-Life Seizures is Reversed by Bumetanide

PubMed Central

Holmes, Gregory L.; Tian, Chengju; Hernan, Amanda E.; Flynn, Sean; Camp, Devon; Barry, Jeremy

2015-01-01

There is a well-described association between infantile epilepsy and pervasive cognitive and behavioral deficits, including a high incidence of autism spectrum disorders. Despite the robustness of the relationship between early-life seizures and the development of autism, the pathophysiological mechanism by which this occurs has not been explored. As a result of increasing evidence that autism is a disorder of brain connectivity we hypothesized that early-life seizures would interrupt normal brain connectivity during brain maturation and result in an autistic phenotype. Normal rat pups underwent recurrent flurothyl-induced seizures from postnatal (P) day 5-14 and then tested, along with controls, for developmental alterations of development brain oscillatory activity from P18-25. Specifically we wished to understand how normal changes in rhythmicity in and between brain regions change as a function of age and if this rhythmicity is altered or interrupted by early life seizures. In rat pups with early-life seizures, field recordings from dorsal and ventral hippocampus and prefrontal cortex demonstrated marked increase in coherence as well as a decrease in voltage correlation at all bandwidths compared to controls while there were minimal differences in total power and relative power spectral densities. Rats with early-life seizures had resulting impairment in the sociability and social novelty tests but demonstrated no evidence of increased activity or generalized anxiety as measured in the open field. In addition, rats with early-life seizures had lower seizure thresholds than controls, indicating long-standing alterations in the excitatory/inhibition balance. Bumetanide, a pharmacological agent that blocks the activity of NKCC1 and induces a significant shift of ECl toward more hyperpolarized values, administration at the time of the seizures precluded the subsequent abnormalities in coherence and voltage correlation and resulted in normal sociability and seizure threshold. Taken together these findings indicate that early-life seizures alter the development of oscillations and result in autistic-like behaviors. The altered communication between these brain regions could reflect the physiological underpinnings underlying social cognitive deficits seen in autism spectrum disorders. PMID:25766676

A rare de novo interstitial duplication of 15q15.3q21.2 in a boy with severe short stature, hypogonadism, global developmental delay and intellectual disability.

PubMed

Yuan, Haiming; Meng, Zhe; Zhang, Lina; Luo, Xiangyang; Liu, Liping; Chen, Mengfan; Li, Xinwei; Zhao, Weiwei; Liang, Liyang

2016-01-01

Interstitial duplications distal to 15q13 are very rare. Here, we reported a 14-year-old boy with severe short stature, delayed bone age, hypogonadism, global developmental delay and intellectual disability. His had distinctive facial features including macrocephaly, broad forehead, deep-set and widely spaced eyes, broad nose bridge, shallow philtrum and thick lips. A de novo 6.4 Mb interstitial duplication of 15q15.3q21.2 was detected by chromosomal microarray analysis. We compared our patient's clinical phenotypes with those of several individuals with overlapping duplications and several candidate genes responsible for the phenotypes were identified as well. The results suggest a novel contiguous gene duplication syndrome characterized with shared features including short stature, hypogonadism, global developmental delay and other congenital anomalies.

Behavioral characteristics of very-low-birth-weight infants of varying biologic risk at 6, 15, and 24 months of age.

PubMed

Oehler, J M; Thompson, R J; Goldstein, R F; Gustafson, K E; Brazy, J E

1996-01-01

To explore the relationship between developmental outcome and behavior of very-low-birth-weight (VLBW) infants (< or = 1500 g) at high and low biologic risk. Descriptive, ex post facto. Clinic for follow-up of infants at high risk. A convenience sample of 102 VLBW infants, free of major congenital anomalies, who completed 6-, 15-, and 24-month developmental testing and who were part of a larger study of 274 VLBW infants. Bayley Scales of Infant Development. Infants at high biologic risk, versus infants at low biologic risk, were less attentive and active through age 15 months and were less adept in gross and fine motor skills through age 24 months (p < or = 0.05-0.001). Infants with continuous delay were less attentive than infants with no delay or late delay through age 24 months, less active through age 15 months (p < or = 0.001-0.001), and less skilled in motor behaviors through age 24 months (p < or = 0.05-0.001). Infants at high biologic risk and infants with developmental delays are less attentive, less active, and less skilled in motor tasks during the first 15-24 months of life, suggesting an association between biologic risk and behavior and developmental delay and behavior.

DISCRIMINATION ACQUISITION IN CHILDREN WITH DEVELOPMENTAL DISABILITIES UNDER IMMEDIATE AND DELAYED REINFORCEMENT

PubMed Central

Sy, Jolene R.; Vollmer, Timothy R.

2012-01-01

We evaluated the discrimination acquisition of individuals with developmental disabilities under immediate and delayed reinforcement. In Experiment 1, discrimination between two alternatives was examined when reinforcement was immediate or delayed by 20 s, 30 s, or 40 s. In Experiment 2, discrimination between 2 alternatives was compared across an immediate reinforcement condition and a delayed reinforcement condition in which subjects could respond during the delay. In Experiment 3, discrimination among 4 alternatives was compared across immediate and delayed reinforcement. In Experiment 4, discrimination between 2 alternatives was examined when reinforcement was immediate and 0-s or 30-s intertrial intervals (ITI) were programmed. For most subjects, discrimination acquisition occurred under immediate reinforcement. However, for some subjects, introducing delays slowed or prevented discrimination acquisition under some conditions. Results from Experiment 4 suggest that longer ITIs cannot account for the lack of discrimination under delayed reinforcement. PMID:23322925

The impact of methylphenidate on seizure frequency and severity in children with attention-deficit-hyperactivity disorder and difficult-to-treat epilepsies.

PubMed

Santos, Kleber; Palmini, Andre; Radziuk, Ana L; Rotert, Rosana; Bastos, Fernanda; Booij, Linda; Fernandes, Brisa S

2013-07-01

Difficult-to-treat epilepsies and attention-deficit-hyperactivity disorder (ADHD) often co-occur. Because of concerns about the use of stimulants in children with this comorbidity, the impact of ADHD treatment on seizure frequency and severity is not known. This pilot study evaluated the safety and efficacy of methylphenidate in this population. After a 3 month period in which antiepileptic drugs were adjusted, 22 patients recruited from a specialist outpatient clinic for severe epilepsy (16 males, six females; mean age 11 y 2 mo, SD 3 y 2 mo) received methylphenidate for 3 months in an open label, non-controlled trial; four with generalized or multifocal (symptomatic/cryptogenic) epilepsy, one with generalized (idiopathic) epilepsy, 17 with partial (symptomatic/cryptogenic) epilepsy; five with partial seizures only, 17 with primarily or secondarily generalized seizures). Epilepsy, ADHD symptoms, and side effects were assessed using the Swanson, Nolan, and Pelham Questionnaire, the Child Behavior Checklist, the Hague Seizure Severity Scale, and the Side Effects Rating Scale. Methylphenidate significantly improved ADHD. After 3 months of treatment, 73% of patients no longer had clinically significant symptoms. Methylphenidate also reduced seizure severity (9-point median decrease on the Hague Seizure Severity Scale). Seizure frequency increased in four out of 22 patients, but only one patient withdrew from the study for this reason. Most patients experienced no major side effects. These data are among the first showing that low doses of methylphenidate are safe and effective to treat ADHD symptoms in patients with difficult-to-treat epilepsies. Randomized controlled trials are needed to replicate the findings. © The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.

Immunomodulatory effect of Celecoxib on HMGB1/TLR4 pathway in a recurrent seizures model in immature rats.

PubMed

Morales-Sosa, Mariana; Orozco-Suárez, Sandra; Vega-García, Angélica; Caballero-Chacón, Sara; Feria-Romero, Iris A

2018-07-01

Epileptic seizures constitute an important problem in pediatric neurology during the developmental period. The frequency and nosological significance of seizures, as well as their association with epileptogenesis, may be related to underlying mechanisms such as neuroinflammation. Those mechanisms of response activate inflammatory molecules induced in the neurons, activated glial cells and endothelial cells via the key HMGB1/TLR4 pathway. In this study, the drug celecoxib (CCX) was used as a blocker of the cyclooxygenase 2 (COX-2) and HMGB1/TLR-4 pathways. The experimental model was implemented in 10-day-old neonatal Sprague Dawley rats to induce recurrent seizures with kainic acid (KA, 1.4 mg/kg). Data were evaluated at early (14 PND) and late (30 PND) time points. The results showed that the CCX and CCX + pentobarbital (PB) groups exhibited a protective effect by significantly increasing the time latency of seizures compared to the KA group at both early (p < 0.01) and late (p < 0.001) times. When the CCX group was compared to the KA group, there was also a significant decrease in the number of HMGB1 and TLR-4 transcripts (p < 0.05) and in COX-2 protein expression (p < 0.05) in the most important areas for seizure generation (the hippocampus and cortex) at both the early and late time points. These results demonstrated that CCX treatment after epileptic seizures has a neuroprotective effect due to the inhibition of proinflammatory proteins and associated signaling pathways and reduces seizure susceptibility. Additionally, the timely intervention of inflammatory pathways will reduce the risk of developing epilepsy in adulthood. Copyright © 2018 Elsevier Inc. All rights reserved.

Prevention of plasticity of endocannabinoid signaling inhibits persistent limbic hyperexcitability caused by developmental seizures.

PubMed

Chen, Kang; Neu, Axel; Howard, Allyson L; Földy, Csaba; Echegoyen, Julio; Hilgenberg, Lutz; Smith, Martin; Mackie, Ken; Soltesz, Ivan

2007-01-03

Depolarization-induced suppression of inhibition (DSI) is an endocannabinoid-mediated short-term plasticity mechanism that couples postsynaptic Ca2+ rises to decreased presynaptic GABA release. Whether the gain of this retrograde synaptic mechanism is subject to long-term modulation by glutamatergic excitatory inputs is not known. Here, we demonstrate that activity-dependent long-term DSI potentiation takes place in hippocampal slices after tetanic stimulation of Schaffer collateral synapses. This activity-dependent, long-term plasticity of endocannabinoid signaling was specific to GABAergic synapses, as it occurred without increases in the depolarization-induced suppression of excitation. Induction of tetanus-induced DSI potentiation in vitro required a complex pathway involving AMPA/kainate and metabotropic glutamate receptor as well as CB1 receptor activation. Because DSI potentiation has been suggested to play a role in persistent limbic hyperexcitability after prolonged seizures in the developing brain, we used these mechanistic insights into activity-dependent DSI potentiation to test whether interference with the induction of DSI potentiation prevents seizure-induced long-term hyperexcitability. The results showed that the in vitro, tetanus-induced DSI potentiation was occluded by previous in vivo fever-induced (febrile) seizures, indicating a common pathway. Accordingly, application of CB1 receptor antagonists during febrile seizures in vivo blocked the seizure-induced persistent DSI potentiation, abolished the seizure-induced upregulation of CB1 receptors, and prevented the emergence of long-term limbic hyperexcitability. These results reveal a new form of activity-dependent, long-term plasticity of endocannabinoid signaling at perisomatic GABAergic synapses, and demonstrate that blocking the induction of this plasticity abolishes the long-term effects of prolonged febrile seizures in the developing brain.

Neuregulin-1 is Neuroprotective in a Rat Model of Organophosphate-Induced Delayed Neuronal Injury

PubMed Central

Li, Yonggang; Lein, Pamela J.; Liu, Cuimei; Bruun, Donald A.; Giulivi, Cecilia; Ford, Gregory; Tewolde, Teclemichael; Ross-Inta, Catherine; Ford, Byron D.

2012-01-01

Current medical countermeasures against organophosphate (OP) nerve agents are effective in reducing mortality, but do not sufficiently protect the CNS from delayed brain damage and persistent neurological symptoms. In this study, we examined the efficacy of neuregulin-1 (NRG-1) in protecting against delayed neuronal cell death following acute intoxication with the OP diisopropylfluorophosphate (DFP). Adult male Sprague Dawley rats were pretreated with pyridostigmine (0.1 mg/kg BW, i.m.) and atropine methylnitrate (20 mg/kg BW, i.m.) prior to DFP (9 mg/kg BW, i.p.) intoxication to increase survival and reduce peripheral signs of cholinergic toxicity but not prevent DFP-induced seizures or delayed neuronal injury. Pretreatment with NRG-1 did not protect against seizures in rats exposed to DFP. However, neuronal injury was significantly reduced in most brain regions by pretreatment with NRG-1 isoforms NRG-EGF (3.2 μg/kg BW, i.a) or NRG-GGF2 (48 μg/kg BW, i.a.) as determined by FluroJade-B labeling in multiple brain regions at 24 h post-DFP injection. NRG-1 also blocked apoptosis and oxidative stress-mediated protein damage in the brains of DFP-intoxicated rats. Administration of NRG-1 at 1 h after DFP injection similarly provided significant neuroprotection against delayed neuronal injury. These findings identify NRG-1 as a promising adjuvant therapy to current medical countermeasures for enhancing neuroprotection against acute OP intoxication. PMID:22583949

Attention and material-specific memory in children with lateralized epilepsy.

PubMed

Engle, Jennifer A; Smith, Mary Lou

2010-01-01

Epilepsy is frequently associated with attention and memory problems. In adults, lateralization of seizure focus impacts the type of memory affected (left-sided lesions primarily impact verbal memory, while right-sided lesions primarily impact visual memory), but the relationship between seizure focus and the nature of the memory impairment is less clear in children. The current study examines the correlation between parent-reported attention problems and material-specific memory (verbal or visual-spatial) in 65 children (ages 6-16) with medically intractable lateralized epilepsy. There were no significant differences in attention and memory between those with left-lateralized epilepsy (n=25) and those with right-lateralized epilepsy (n=40). However, in the left-lateralized group attention problems were significantly negatively correlated only with delayed visual memory (r=-.450, p<.05), while the right-lateralized group demonstrated the opposite pattern (attention problems significantly negatively correlated with delayed verbal memory; r=-.331, p<.05). These findings suggest that lateralization of seizure focus may in fact impact children's memory in a material-specific manner, while problems with attention may impact memory more globally. Therefore, interventions designed to improve attention in children with epilepsy may have utility in improving certain aspects of memory, but further suggest that in children with lateralized epilepsy, material-specific memory deficits may not resolve with such interventions.

Critical dynamics of Hopf bifurcations in the corticothalamic system: Transitions from normal arousal states to epileptic seizures.

PubMed

Yang, Dong-Ping; Robinson, P A

2017-04-01

A physiologically based corticothalamic model of large-scale brain activity is used to analyze critical dynamics of transitions from normal arousal states to epileptic seizures, which correspond to Hopf bifurcations. This relates an abstract normal form quantitatively to underlying physiology that includes neural dynamics, axonal propagation, and time delays. Thus, a bridge is constructed that enables normal forms to be used to interpret quantitative data. The normal form of the Hopf bifurcations with delays is derived using Hale's theory, the center manifold theorem, and normal form analysis, and it is found to be explicitly expressed in terms of transfer functions and the sensitivity matrix of a reduced open-loop system. It can be applied to understand the effect of each physiological parameter on the critical dynamics and determine whether the Hopf bifurcation is supercritical or subcritical in instabilities that lead to absence and tonic-clonic seizures. Furthermore, the effects of thalamic and cortical nonlinearities on the bifurcation type are investigated, with implications for the roles of underlying physiology. The theoretical predictions about the bifurcation type and the onset dynamics are confirmed by numerical simulations and provide physiologically based criteria for determining bifurcation types from first principles. The results are consistent with experimental data from previous studies, imply that new regimes of seizure transitions may exist in clinical settings, and provide a simplified basis for control-systems interventions. Using the normal form, and the full equations from which it is derived, more complex dynamics, such as quasiperiodic cycles and saddle cycles, are discovered near the critical points of the subcritical Hopf bifurcations.

Critical dynamics of Hopf bifurcations in the corticothalamic system: Transitions from normal arousal states to epileptic seizures

NASA Astrophysics Data System (ADS)

Yang, Dong-Ping; Robinson, P. A.

2017-04-01

A physiologically based corticothalamic model of large-scale brain activity is used to analyze critical dynamics of transitions from normal arousal states to epileptic seizures, which correspond to Hopf bifurcations. This relates an abstract normal form quantitatively to underlying physiology that includes neural dynamics, axonal propagation, and time delays. Thus, a bridge is constructed that enables normal forms to be used to interpret quantitative data. The normal form of the Hopf bifurcations with delays is derived using Hale's theory, the center manifold theorem, and normal form analysis, and it is found to be explicitly expressed in terms of transfer functions and the sensitivity matrix of a reduced open-loop system. It can be applied to understand the effect of each physiological parameter on the critical dynamics and determine whether the Hopf bifurcation is supercritical or subcritical in instabilities that lead to absence and tonic-clonic seizures. Furthermore, the effects of thalamic and cortical nonlinearities on the bifurcation type are investigated, with implications for the roles of underlying physiology. The theoretical predictions about the bifurcation type and the onset dynamics are confirmed by numerical simulations and provide physiologically based criteria for determining bifurcation types from first principles. The results are consistent with experimental data from previous studies, imply that new regimes of seizure transitions may exist in clinical settings, and provide a simplified basis for control-systems interventions. Using the normal form, and the full equations from which it is derived, more complex dynamics, such as quasiperiodic cycles and saddle cycles, are discovered near the critical points of the subcritical Hopf bifurcations.

Systems biology of human epilepsy applied to patients with brain tumors.

PubMed

Mittal, Sandeep; Shah, Aashit K; Barkmeier, Daniel T; Loeb, Jeffrey A

2013-12-01

Epilepsy is a disease of recurrent seizures that can be associated with a wide variety of acquired and developmental brain lesions. Current medications for patients with epilepsy can suppress seizures; they do not cure or modify the underlying disease process. On the other hand, surgical removal of focal brain regions that produce seizures can be curative. This surgical procedure can be more precise with the placement of intracranial recording electrodes to identify brain regions that generate seizure activity as well as those that are critical for normal brain function. The detail that goes into these surgeries includes extensive neuroimaging, electrophysiology, and clinical data. Combined with precisely localized tissues removed, these data provide an unparalleled opportunity to learn about the interrelationships of many "systems" in the human brain not possible in just about any other human brain disorder. Herein, we describe a systems biology approach developed to study patients who undergo brain surgery for epilepsy and how we have begun to apply these methods to patients whose seizures are associated with brain tumors. A central goal of this clinical and translational research program is to improve our understanding of epilepsy and brain tumors and to improve diagnosis and treatment outcomes of both. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Recall Memory in Children with Down Syndrome and Typically Developing Peers Matched on Developmental Age

ERIC Educational Resources Information Center

Milojevich, H.; Lukowski, A.

2016-01-01

Background: Whereas research has indicated that children with Down syndrome (DS) imitate demonstrated actions over short delays, it is presently unknown whether children with DS recall information over lengthy delays at levels comparable with typically developing (TD) children matched on developmental age. Method: In the present research, 10…

Divergent Development of Gross Motor Skills in Children Who Are Blind or Sighted

ERIC Educational Resources Information Center

Brambring, Michael

2006-01-01

This empirical study compared the average ages at which four congenitally blind children acquired 29 gross motor skills with age norms for sighted children. The results indicated distinct developmental delays in the acquisition of motor skills and a high degree of variability in developmental delays within and across the six subdomains that were…

Microarray as a First Genetic Test in Global Developmental Delay: A Cost-Effectiveness Analysis

ERIC Educational Resources Information Center

Trakadis, Yannis; Shevell, Michael

2011-01-01

Aim: Microarray technology has a significantly higher clinical yield than karyotyping in individuals with global developmental delay (GDD). Despite this, it has not yet been routinely implemented as a screening test owing to the perception that this approach is more expensive. We aimed to evaluate the effect that replacing karyotype with…

Responsive Interaction Interventions for Children with or at Risk for Developmental Delays: A Research Synthesis

ERIC Educational Resources Information Center

Kong, Na Young; Carta, Judith J.

2013-01-01

The purpose of this article is to synthesize the available studies regarding responsive interaction intervention (RII) for children with or at risk for developmental delays with a focus on six dimensions: (a) the characteristics of participants, (b) the features of RII, (c) the measurement of treatment fidelity, (d) the overall effectiveness of…

State and Jurisdictional Eligibility Definitions for Infants and Toddlers with Disabilities under IDEA. NECTAC Notes.

ERIC Educational Resources Information Center

Shackelford, Jo

Under Part C of the Individuals with Disabilities Education Act (IDEA), participating states and jurisdictions must provide services to children who are either experiencing developmental delays, or who have a diagnosed mental or physical condition that has a a high probability of resulting in developmental delay. Additionally, states may choose to…

State and Jurisdictional Eligibility Definitions for Infants and Toddlers with Disabilities under IDEA. NECTAC Notes No. 16

ERIC Educational Resources Information Center

Shackelford, Jo

2004-01-01

Under Part C of the Individuals with Disabilities Education Act (IDEA), participating states and jurisdictions must provide services to children who are either experiencing developmental delays, or who have a diagnosed mental or physical condition that has a high probability of resulting in developmental delay. Additionally, states may choose to…

The Positive Impact of Early Intervention for Children with Developmental Delays, Gestational Cocaine Exposure, and Co-Occurring Risk Factors

ERIC Educational Resources Information Center

Ullery, Mary Anne; Katz, Lynne

2017-01-01

This article examined transition rates of young children (n = 102) from an early intervention program at the Linda Ray Intervention Program (LRIP) who had documented developmental delays and co-occurring prenatal drug exposure often coupled with verified child maltreatment. Findings indicated that there was significant group improvement from…

The Role of Maternal Depression in Accessing Early Intervention Services for Children with Developmental Delay

ERIC Educational Resources Information Center

Colgan, Siobhan Eileen

2012-01-01

This study investigated the relationship between maternal depression and children's access to early intervention services among a sample of children with developmental delay at age two who were determined to be eligible for early intervention services, were full term and of normal birth weight, and were not previously identified with any special…

Divergent Development of Verbal Skills in Children Who Are Blind or Sighted

ERIC Educational Resources Information Center

Journal of Visual Impairment & Blindness, 2007

2007-01-01

This empirical study compared the average ages at which four children with congenital blindness acquired 29 verbal skills with given age norms for sighted children. The results indicated only small developmental delays in the acquisition of verbal skills in the four children, but a high degree of variability in developmental delays within and…

Motivational Climate, Motor-Skill Development, and Perceived Competence: Two Studies of Developmentally Delayed Kindergarten Children

ERIC Educational Resources Information Center

Valentini, Nadia; Rudisill, Mary E.

2004-01-01

Two studies were conducted to examine the effects of motivational climate on motor-skill development and perceived physical competence in kindergarten children with developmental delays. In Experiment 1, two intervention groups were exposed to environments with either high (mastery climate) or low autonomy for 12 weeks. Results showed that the…

A Case-Controlled Investigation of Tactile Reactivity in Young Children with and without Global Developmental Delay

ERIC Educational Resources Information Center

Barney, Chantel C.; Tervo, Raymond; Wilcox, George L.; Symons, Frank J.

2017-01-01

Assessing tactile function among children with intellectual, motor, and communication impairments remains a clinical challenge. A case control design was used to test whether children with global developmental delays (GDD; n = 20) would be more/less reactive to a modified quantitative sensory test (mQST) compared to controls (n = 20). Reactivity…

Motor Skill Interventions to Improve Fundamental Movement Skills of Preschoolers with Developmental Delay

ERIC Educational Resources Information Center

Kirk, Megan A.; Rhodes, Ryan E.

2011-01-01

Preschoolers with developmental delay (DD) are at risk for poor fundamental movement skills (FMS), but a paucity of early FMS interventions exist. The purpose of this review was to critically appraise the existing interventions to establish direction for future trials targeting preschoolers with DD. A total of 11 studies met the inclusion…

Introduction to Sexuality Education for Individuals Who Are Deaf-Blind and Significantly Developmentally Delayed.

ERIC Educational Resources Information Center

Moss, Kate; Blaha, Robbie

The ten chapters of this book address sexuality issues in the lives of school age individuals who are deaf-blind or significantly developmentally delayed. It notes that these individuals usually do not experience sexuality through typical relationships and thus require a different type of instruction. Chapters have the following titles: (1)…

Divergent Development of Manual Skills in Children Who Are Blind or Sighted

ERIC Educational Resources Information Center

Brambring, Michael

2007-01-01

This empirical study compared the average ages at which four children with congenital blindness acquired 32 fine motor skills with age norms for sighted children. The results indicated that the children experienced extreme developmental delays in the acquisition of manual skills and a high degree of variability in developmental delays within and…

A 20 Year Review of Punishment and Alternative Methods to Treat Problem Behaviors in Developmentally Delayed Persons.

ERIC Educational Resources Information Center

Matson, Johnny L.; Taras, Marie E.

1989-01-01

Studies assessing treatments for severe behavior problems of developmentally delayed persons were reviewed. Procedures used in the 382 studies, published from 1967-1987, were analyzed in terms of problem behaviors, side effects, and treatment methods. Also examined were number of studies reported yearly, maintenance and generalization of effects,…

Small Steps: An Early Intervention Program for Children with Developmental Delays.

ERIC Educational Resources Information Center

Pieterse, Moira; And Others

This boxed set includes eight booklets of home activities for early intervention for young children with developmental delays. The first book provides an introduction to the program and its implementation, lists 23 resources, describes a videotape which supplements the booklets, and includes a glossary. Book 2 covers how to select goals for the…

De novo interstitial deletion of 3q22.3-q25.2 encompassing FOXL2, ATR, ZIC1, and ZIC4 in a patient with blepharophimosis/ptosis/epicanthus inversus syndrome, Dandy-Walker malformation, and global developmental delay.

PubMed

Lim, Byung Chan; Park, Woong Yang; Seo, Eul-Ju; Kim, Ki Joong; Hwang, Yong Seung; Chae, Jong Hee

2011-05-01

We report a case carrying a de novo interstitial deletion of chromosome 3q22-q25. The clinical phenotype of this case included blepharophimosis/ptosis/epicanthus inversus syndrome, Dandy-Walker malformation, and global developmental delay. Contiguous heterozygous deletion of FOXL2, ATR, ZIC1, and ZIC4 was postulated as the causative mechanism of the clinical phenotype. The association of blepharophimosis, ptosis, and epicanthus inversus syndrome with developmental delay or mental retardation may be an indication for the use of brain imaging and chromosomal analysis capable of detecting chromosomal rearrangements encompassing several candidate genes.

Audiogenic seizure activity following HSV-1 GAD65 sense or antisense injection into inferior colliculus of Long-Evans rat.

PubMed

Coleman, James R; Thompson, Karen C; Wilson, Marlene A; Wilson, Steven P

2017-06-01

Herpes virus technology involving manipulation of GAD65 was used to study effects on audiogenic seizures (AGS). Audiogenic seizure behaviors were examined following injections of replication-defective herpes simplex virus (HSV-1) vectors incorporating sense or antisense toward GAD65 along with 10% lac-Z into the central nucleus of inferior colliculus (CNIC) of Long-Evans rats. In seizure-sensitive animals developmentally primed by intense sound exposure, injection of GAD65 in the sense orientation increased wild running latencies and reduced incidence of clonus compared with lac-Z only, unoperated, and vehicle seizure groups. In contrast, infection of CNIC with GAD65 antisense virus resulted in 100% incidence of wild running and clonus behaviors in AGS animals. Unprimed animals not operated continued to show uniform absence of seizure activity. Administration of GAD65 antisense virus into CNIC produced novel wild running and clonus behaviors in some unprimed animals. Staining for β-galactosidase in all vector animals revealed no differences in pattern or numbers of immunoreactive cells at injection sites. Qualitatively, typical small and medium multipolar/stellate and medium fusiform neurons appeared in the CNIC of vector animals. These results demonstrate that HSV-1 vector constructs implanted into the CNIC can predictably influence incidence and severity of AGS and suggest that viral vectors can be useful in studying GABA mechanisms with potential for therapeutic application in epilepsy. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". Copyright © 2016 Elsevier Inc. All rights reserved.

Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, exerts antiepileptic effects via the GABA/benzodiazepine receptor complex in mice

PubMed Central

Chen, CR; Tan, R; Qu, WM; Wu, Z; Wang, Y; Urade, Y; Huang, ZL

2011-01-01

BACKGROUND AND PURPOSE The aim of this study was to evaluate the anti-convulsant effects of magnolol (6, 6′, 7, 12-tetramethoxy-2, 2′-dimethyl-1-β-berbaman, C18H18O2) and the mechanisms involved. EXPERIMENTAL APPROACH Mice were treated with magnolol (20, 40 and 80 mg·kg−1) 30 min before injection with pentylenetetrazol (PTZ, 60 mg·kg−1, i.p.). The anti-seizure effects of magnolol were analysed using seizure models of behaviour, EEG and in vitro electrophysiology and c-Fos expression in the hippocampus and cortex. KEY RESULTS Magnolol at doses of 40 and 80 mg·kg−1 significantly delayed the onset of myoclonic jerks and generalized clonic seizures, and decreased the seizure stage and mortality compared with those of the vehicle-treated animals. EEG recordings showed that magnolol (40 and 80 mg·kg−1) prolonged the latency of seizure onset and decreased the number of seizure spikes. The anti-epileptic effect of magnolol was reversed by the GABAA/benzodiazepine receptor antagonist flumazenil. Pretreatment with flumazenil decreased the effects of magnolol on prolongation of seizure latency and decline of seizure stage. In a Mg2+-free model of epileptiform activity, using multi-electrode array recordings in mouse hippocampal slices, magnolol decreased spontaneous epileptiform discharges. Magnolol also significantly decreased seizure-induced Fos immunoreactivity in the piriform cortex, dentate gyrus and hippocampal area CA1. These effects were attenuated by pretreatment with flumazenil. CONCLUSIONS AND IMPLICATIONS These findings indicate that the inhibitory effects of magnolol on epileptiform activity were mediated by the GABAA/benzodiazepine receptor complex. PMID:21518336

Optimized Seizure Detection Algorithm: A Fast Approach for Onset of Epileptic in EEG Signals Using GT Discriminant Analysis and K-NN Classifier

PubMed Central

Rezaee, Kh.; Azizi, E.; Haddadnia, J.

2016-01-01

Background Epilepsy is a severe disorder of the central nervous system that predisposes the person to recurrent seizures. Fifty million people worldwide suffer from epilepsy; after Alzheimer’s and stroke, it is the third widespread nervous disorder. Objective In this paper, an algorithm to detect the onset of epileptic seizures based on the analysis of brain electrical signals (EEG) has been proposed. 844 hours of EEG were recorded form 23 pediatric patients consecutively with 163 occurrences of seizures. Signals had been collected from Children’s Hospital Boston with a sampling frequency of 256 Hz through 18 channels in order to assess epilepsy surgery. By selecting effective features from seizure and non-seizure signals of each individual and putting them into two categories, the proposed algorithm detects the onset of seizures quickly and with high sensitivity. Method In this algorithm, L-sec epochs of signals are displayed in form of a third-order tensor in spatial, spectral and temporal spaces by applying wavelet transform. Then, after applying general tensor discriminant analysis (GTDA) on tensors and calculating mapping matrix, feature vectors are extracted. GTDA increases the sensitivity of the algorithm by storing data without deleting them. Finally, K-Nearest neighbors (KNN) is used to classify the selected features. Results The results of simulating algorithm on algorithm standard dataset shows that the algorithm is capable of detecting 98 percent of seizures with an average delay of 4.7 seconds and the average error rate detection of three errors in 24 hours. Conclusion Today, the lack of an automated system to detect or predict the seizure onset is strongly felt. PMID:27672628

An Excitatory Loop with Astrocytes Contributes to Drive Neurons to Seizure Threshold

PubMed Central

Chiavegato, Angela; Zonta, Micaela; Cammarota, Mario; Brondi, Marco; Vetri, Francesco; Uva, Laura; Pozzan, Tullio; de Curtis, Marco; Ratto, Gian Michele; Carmignoto, Giorgio

2010-01-01

Seizures in focal epilepsies are sustained by a highly synchronous neuronal discharge that arises at restricted brain sites and subsequently spreads to large portions of the brain. Despite intense experimental research in this field, the earlier cellular events that initiate and sustain a focal seizure are still not well defined. Their identification is central to understand the pathophysiology of focal epilepsies and to develop new pharmacological therapies for drug-resistant forms of epilepsy. The prominent involvement of astrocytes in ictogenesis was recently proposed. We test here whether a cooperation between astrocytes and neurons is a prerequisite to support ictal (seizure-like) and interictal epileptiform events. Simultaneous patch-clamp recording and Ca2+ imaging techniques were performed in a new in vitro model of focal seizures induced by local applications of N-methyl-D-aspartic acid (NMDA) in rat entorhinal cortex slices. We found that a Ca2+ elevation in astrocytes correlates with both the initial development and the maintenance of a focal, seizure-like discharge. A delayed astrocyte activation during ictal discharges was also observed in other models (including the whole in vitro isolated guinea pig brain) in which the site of generation of seizure activity cannot be precisely monitored. In contrast, interictal discharges were not associated with Ca2+ changes in astrocytes. Selective inhibition or stimulation of astrocyte Ca2+ signalling blocked or enhanced, respectively, ictal discharges, but did not affect interictal discharge generation. Our data reveal that neurons engage astrocytes in a recurrent excitatory loop (possibly involving gliotransmission) that promotes seizure ignition and sustains the ictal discharge. This neuron–astrocyte interaction may represent a novel target to develop effective therapeutic strategies to control seizures. PMID:20405049

Insomnia in epilepsy is associated with continuing seizures and worse quality of life.

PubMed

Quigg, Mark; Gharai, Sean; Ruland, Jeff; Schroeder, Catherine; Hodges, Matthew; Ingersoll, Karen S; Thorndike, Frances P; Yan, Guofen; Ritterband, Lee M

2016-05-01

To evaluate how insomnia is associated with seizure control and quality of life in patients with epilepsy. Consecutive patients with epilepsy attending clinical visits were surveyed with the Insomnia Severity Index (ISI). Patients had to be treated with at least one anticonvulsant and could not have had documented psychogenic pseudoseizure. The presence or absence of seizures and quality of life (QOLIE-P-10) within the past 4 weeks was recorded. Other variables included demographic and clinical data, sleep-wake timing, the Hörne-Östberg Morningness-Eveningness Questionnaire (MEQ), sleepiness (Epworth Sleepiness Scale (ESS), and mood (Center for Epidemiologic Studies Depression Scale, CES-D). 207 patients completed surveys. 43% had clinically significant insomnia, and 51% had at least mild insomnia. 58% were seizure free. Mean ISI scores were significantly worse for those with continuing seizures, and more severe ISI scores correlated strongly with worse QOL. Younger age, shorter duration of epilepsy, use of sedative/hypnotics, medical and sleep comorbidities, delayed sleep timing and chronotype, excessive sleepiness, and depression were all associated with more severe insomnia. Those with unexpected health care visits over the most recent 4 weeks had worse insomnia. After adjustment for these covariates, more severe insomnia remained significantly associated with lack of seizure freedom and with worse QOL. Insomnia is common in epilepsy, and is associated with short term poor seizure control and worse QOL. Future studies must evaluate cause-and-effect relationships. Assessment of insomnia may be important in the comprehensive care of epilepsy and may influence control of epileptic seizures. Copyright © 2016 Elsevier B.V. All rights reserved.

The phenotypic spectrum of SCN8A encephalopathy

PubMed Central

Larsen, Jan; Carvill, Gemma L.; Gardella, Elena; Kluger, Gerhard; Schmiedel, Gudrun; Barisic, Nina; Depienne, Christel; Brilstra, Eva; Mang, Yuan; Nielsen, Jens Erik Klint; Kirkpatrick, Martin; Goudie, David; Goldman, Rebecca; Jähn, Johanna A.; Jepsen, Birgit; Gill, Deepak; Döcker, Miriam; Biskup, Saskia; McMahon, Jacinta M.; Koeleman, Bobby; Harris, Mandy; Braun, Kees; de Kovel, Carolien G.F.; Marini, Carla; Specchio, Nicola; Djémié, Tania; Weckhuysen, Sarah; Tommerup, Niels; Troncoso, Monica; Troncoso, Ledia; Bevot, Andrea; Wolff, Markus; Hjalgrim, Helle; Guerrini, Renzo; Møller, Rikke S.

2015-01-01

Objective: SCN8A encodes the sodium channel voltage-gated α8-subunit (Nav1.6). SCN8A mutations have recently been associated with epilepsy and neurodevelopmental disorders. We aimed to delineate the phenotype associated with SCN8A mutations. Methods: We used high-throughput sequence analysis of the SCN8A gene in 683 patients with a range of epileptic encephalopathies. In addition, we ascertained cases with SCN8A mutations from other centers. A detailed clinical history was obtained together with a review of EEG and imaging data. Results: Seventeen patients with de novo heterozygous mutations of SCN8A were studied. Seizure onset occurred at a mean age of 5 months (range: 1 day to 18 months); in general, seizures were not triggered by fever. Fifteen of 17 patients had multiple seizure types including focal, tonic, clonic, myoclonic and absence seizures, and epileptic spasms; seizures were refractory to antiepileptic therapy. Development was normal in 12 patients and slowed after seizure onset, often with regression; 5 patients had delayed development from birth. All patients developed intellectual disability, ranging from mild to severe. Motor manifestations were prominent including hypotonia, dystonia, hyperreflexia, and ataxia. EEG findings comprised moderate to severe background slowing with focal or multifocal epileptiform discharges. Conclusion: SCN8A encephalopathy presents in infancy with multiple seizure types including focal seizures and spasms in some cases. Outcome is often poor and includes hypotonia and movement disorders. The majority of mutations arise de novo, although we observed a single case of somatic mosaicism in an unaffected parent. PMID:25568300

The phenotypic spectrum of SCN8A encephalopathy.

PubMed

Larsen, Jan; Carvill, Gemma L; Gardella, Elena; Kluger, Gerhard; Schmiedel, Gudrun; Barisic, Nina; Depienne, Christel; Brilstra, Eva; Mang, Yuan; Nielsen, Jens Erik Klint; Kirkpatrick, Martin; Goudie, David; Goldman, Rebecca; Jähn, Johanna A; Jepsen, Birgit; Gill, Deepak; Döcker, Miriam; Biskup, Saskia; McMahon, Jacinta M; Koeleman, Bobby; Harris, Mandy; Braun, Kees; de Kovel, Carolien G F; Marini, Carla; Specchio, Nicola; Djémié, Tania; Weckhuysen, Sarah; Tommerup, Niels; Troncoso, Monica; Troncoso, Ledia; Bevot, Andrea; Wolff, Markus; Hjalgrim, Helle; Guerrini, Renzo; Scheffer, Ingrid E; Mefford, Heather C; Møller, Rikke S

2015-02-03

SCN8A encodes the sodium channel voltage-gated α8-subunit (Nav1.6). SCN8A mutations have recently been associated with epilepsy and neurodevelopmental disorders. We aimed to delineate the phenotype associated with SCN8A mutations. We used high-throughput sequence analysis of the SCN8A gene in 683 patients with a range of epileptic encephalopathies. In addition, we ascertained cases with SCN8A mutations from other centers. A detailed clinical history was obtained together with a review of EEG and imaging data. Seventeen patients with de novo heterozygous mutations of SCN8A were studied. Seizure onset occurred at a mean age of 5 months (range: 1 day to 18 months); in general, seizures were not triggered by fever. Fifteen of 17 patients had multiple seizure types including focal, tonic, clonic, myoclonic and absence seizures, and epileptic spasms; seizures were refractory to antiepileptic therapy. Development was normal in 12 patients and slowed after seizure onset, often with regression; 5 patients had delayed development from birth. All patients developed intellectual disability, ranging from mild to severe. Motor manifestations were prominent including hypotonia, dystonia, hyperreflexia, and ataxia. EEG findings comprised moderate to severe background slowing with focal or multifocal epileptiform discharges. SCN8A encephalopathy presents in infancy with multiple seizure types including focal seizures and spasms in some cases. Outcome is often poor and includes hypotonia and movement disorders. The majority of mutations arise de novo, although we observed a single case of somatic mosaicism in an unaffected parent. © 2015 American Academy of Neurology.

Cross-species pharmacological characterization of the allylglycine seizure model in mice and larval zebrafish.

PubMed

Leclercq, Karine; Afrikanova, Tatiana; Langlois, Melanie; De Prins, An; Buenafe, Olivia E; Rospo, Chiara C; Van Eeckhaut, Ann; de Witte, Peter A M; Crawford, Alexander D; Smolders, Ilse; Esguerra, Camila V; Kaminski, Rafal M

2015-04-01

Treatment-resistant seizures affect about a third of patients suffering from epilepsy. To fulfill the need for new medications targeting treatment-resistant seizures, a number of rodent models offer the opportunity to assess a variety of potential treatment approaches. The use of such models, however, has proven to be time-consuming and labor-intensive. In this study, we performed pharmacological characterization of the allylglycine (AG) seizure model, a simple in vivo model for which we demonstrated a high level of treatment resistance. (d,l)-Allylglycine inhibits glutamic acid decarboxylase (GAD) - the key enzyme in γ-aminobutyric acid (GABA) biosynthesis - leading to GABA depletion, seizures, and neuronal damage. We performed a side-by-side comparison of mouse and zebrafish acute AG treatments including biochemical, electrographic, and behavioral assessments. Interestingly, seizure progression rate and GABA depletion kinetics were comparable in both species. Five mechanistically diverse antiepileptic drugs (AEDs) were used. Three out of the five AEDs (levetiracetam, phenytoin, and topiramate) showed only a limited protective effect (mainly mortality delay) at doses close to the TD50 (dose inducing motor impairment in 50% of animals) in mice. The two remaining AEDs (diazepam and sodium valproate) displayed protective activity against AG-induced seizures. Experiments performed in zebrafish larvae revealed behavioral AED activity profiles highly analogous to those obtained in mice. Having demonstrated cross-species similarities and limited efficacy of tested AEDs, we propose the use of AG in zebrafish as a convenient and high-throughput model of treatment-resistant seizures. Copyright © 2015 Elsevier Inc. All rights reserved.

Intranasal midazolam during presurgical epilepsy monitoring is well tolerated, delays seizure recurrence, and protects from generalized tonic-clonic seizures.

PubMed

Kay, Lara; Reif, Philipp S; Belke, Marcus; Bauer, Sebastian; Fründ, Detlef; Knake, Susanne; Rosenow, Felix; Strzelczyk, Adam

2015-09-01

To evaluate the tolerability and efficacy of the ictal and immediate postictal application of intranasal midazolam (in-MDZ) in adolescents and adults during video-electroencephalography (EEG) monitoring. Medical records of all patients treated with in-MDZ between 2008 and 2014 were reviewed retrospectively. For each single patient, the time span until recurrence of seizures was analyzed after an index seizure with and without in-MDZ application. To prevent potential bias, we defined the first seizure with application of in-MDZ as the in-MDZ index seizure. The control index seizure was the preceding, alternatively the next successive seizure without application of in-MDZ. In total, 75 epilepsy patients (mean age 34 ± 14.7 years; 42 male, 33 female) were treated with in-MDZ (mean dose 5.1 mg). Adverse events were observed in four patients (5.3%), and no serious adverse events occurred. The median time after EEG seizure onset before administration of in-MDZ was 2.17 min (interquartile range [IQR] 03.82; range 0.13-15.0 min). Over the next 12 h after in-MDZ, the number of seizures was significantly lower (p = 0.031). The median seizure-free interval was significantly longer following treatment with in-MDZ (5.83 h; IQR 6.83, range 0.4-23.87) than it was for those with no in-MDZ treatment (2.37 h; IQR 4.87, range 0.03-21.87; p = 0.015). Conversely, the likelihood of the patient developing a subsequent seizure was four times higher (odds ratio [OR] 4.33, 95% confidence interval [CI] 1.30-14.47) in the first hour and decreased gradually after 12 h (OR 1.5, 95% CI 1.06-2.12). The occurrence of generalized tonic-clonic seizures was lower in the in-MDZ group in the 24-h observation period (OR 4.67, 95% CI 1.41-15.45; p = 0.009). Ictal and immediate postictal administration of in-MDZ was well tolerated and not associated with serious adverse events. We demonstrated a significant reduction of subsequent seizures (all seizure types) for a 12 h period and of generalized tonic-clonic seizures for 24 h following in-MDZ. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Transsylvian selective amygdalohippocampectomy in children with hippocampal sclerosis: seizure, intellectual and memory outcome.

PubMed

Beaton, Anne E; Durnford, Andrew; Heffer-Rahn, Phillip E; Kirkham, Fenella; Griffin, Angela; Gray, William P; Gray, W L S

2012-11-01

This study investigates the efficacy of transylvian selective amygdalohippocampectomy (TS SAH) in children with medically intractable epilepsy due to unilateral hippocampal sclerosis. Post-surgical seizure control, intellectual and memory outcomes are examined. This study reports on pre- and post-surgical clinical data from 10 patients who underwent TS SAH between 2002 and 2010 after 24 months follow-up. Pre- and post-operative change in seizure frequency, AED use, intellect and memory are compared. At 12 months and 24 months post-surgery, 9/10 (90%) and 7/8 (87.5%) patients respectively, were seizure free (Engel I). No patients were classed as Engel III or IV. No significant improvement or decline at a group level was found on measures of intellect or verbal or visual memory. One hundred per cent improved or remained within 1 SD of their pre-operatives score on verbal and perceptual reasoning learning and reasoning measures. Significant improvement was found post-operatively for both immediate and delayed facial memory. Our findings of good post-surgical seizure control and favourable cognitive outcome provides evidence against previous findings that SAH in children may not be effective. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Spontaneous Seizures and Altered Gene Expression in GABA Signaling Pathways in a mind bomb Mutant Zebrafish

PubMed Central

Hortopan, Gabriela A.; Dinday, Matthew T.; Baraban, Scott C.

2010-01-01

Disruption of E3 ubiquitin ligase activity in immature zebrafish mind bomb mutants, leads to a failure in Notch signaling, excessive numbers of neurons, and depletion of neural progenitor cells. This neurogenic phenotype is associated with defects in neural patterning and brain development. Because developmental brain abnormalities are recognized as an important feature of childhood neurological disorders such as epilepsy and autism, we determined whether zebrafish mutants with grossly abnormal brain structure exhibit spontaneous electrical activity that resembles the long-duration, high-amplitude multi-spike discharges reported in immature zebrafish exposed to convulsant drugs. Electrophysiological recordings from agar immobilized mind bomb mutants at three days postfertilization (dpf) confirmed the occurrence of electrographic seizure activity; seizure-like behaviors were also noted during locomotion video tracking of freely behaving mutants. To identify genes differentially expressed in the mind bomb mutant and provide insight into molecular pathways that may mediate these epileptic phenotypes, a transcriptome analysis was performed using microarray. Interesting candidate genes were further analyzed using conventional reverse transcriptasepolymerase chain reaction (RT-PCR) and real-time quantitative PCR (qPCR), as well as whole-mount in situ hybridization. Approximately 150 genes, some implicated in development, transcription, cell metabolism and signal transduction, are differentially regulated including down-regulation of several genes necessary for GABA-mediated signaling. These findings identify a collection of gene transcripts that may be responsible for the abnormal electrical discharge and epileptic activities observed in a mind bomb zebrafish mutant. This work may have important implications for neurological and neurodevelopmental disorders associated with mutations in ubiquitin ligase activity. Notch is an essential component of an evolutionarily conserved signal transduction cascade mediating development. In neuroectoderm, where cells have the potential to become neurons, activated Notch inhibits proneural gene expression in a process referred to as lateral inhibition. In the absence of Notch-mediated lateral inhibition, too many early-born cells differentiate into neurons (Chitnis et al., 1995; de la Pompa et al., 1997). Recent studies identified several E3 ligases that modulate Notch signaling through ubiquitin-dependent protein degradation and endocytosis (Lai, 2002). Ubiquitination, which occurs when an E3 ligase enzyme binds to both substrate and an E2 thioesterified protein (Deshaies and Joazeiro, 2009), is a key mechanism regulating many cellular processes. Mutation or small deletions within the ubiquitin E3A ligase gene in humans has been linked to autism spectrum disorders (Glessner et al., 2009) and Angelman syndrome, a neurogenetic disorder characterized by developmental delay, severe intellectual disability, absent speech, exuberant behavior, motor impairment, and epilepsy (Clayton-Smith and Laan, 2003). PMID:20943912

Analysis of 31-year-old patient with SYNGAP1 gene defect points to importance of variants in broader splice regions and reveals developmental trajectory of SYNGAP1-associated phenotype: case report.

PubMed

Prchalova, Darina; Havlovicova, Marketa; Sterbova, Katalin; Stranecky, Viktor; Hancarova, Miroslava; Sedlacek, Zdenek

2017-06-02

Whole exome sequencing is a powerful tool for the analysis of genetically heterogeneous conditions. The prioritization of variants identified often focuses on nonsense, frameshift and canonical splice site mutations, and highly deleterious missense variants, although other defects can also play a role. The definition of the phenotype range and course of rare genetic conditions requires long-term clinical follow-up of patients. We report an adult female patient with severe intellectual disability, severe speech delay, epilepsy, autistic features, aggressiveness, sleep problems, broad-based clumsy gait and constipation. Whole exome sequencing identified a de novo mutation in the SYNGAP1 gene. The variant was located in the broader splice donor region of intron 10 and replaced G by A at position +5 of the splice site. The variant was predicted in silico and shown experimentally to abolish the regular splice site and to activate a cryptic donor site within exon 10, causing frameshift and premature termination. The overall clinical picture of the patient corresponded well with the characteristic SYNGAP1-associated phenotype observed in previously reported patients. However, our patient was 31 years old which contrasted with most other published SYNGAP1 cases who were much younger. Our patient had a significant growth delay and microcephaly. Both features normalised later, although the head circumference stayed only slightly above the lower limit of the norm. The patient had a delayed puberty. Her cognitive and language performance remained at the level of a one-year-old child even in adulthood and showed a slow decline. Myopathic facial features and facial dysmorphism became more pronounced with age. Although the gait of the patient was unsteady in childhood, more severe gait problems developed in her teens. While the seizures remained well-controlled, her aggressive behaviour worsened with age and required extensive medication. The finding in our patient underscores the notion that the interpretation of variants identified using whole exome sequencing should focus not only on variants in the canonical splice dinucleotides GT and AG, but also on broader splice regions. The long-term clinical follow-up of our patient contributes to the knowledge of the developmental trajectory in individuals with SYNGAP1 gene defects.

Clinical, biochemical, and molecular studies in pyridoxine-dependent epilepsy. Antisense therapy as possible new therapeutic option.

PubMed

Pérez, Belén; Gutiérrez-Solana, Luis González; Verdú, Alfonso; Merinero, Begoña; Yuste-Checa, Patricia; Ruiz-Sala, Pedro; Calvo, Rocio; Jalan, Anil; Marín, Laura López; Campos, Oscar; Ruiz, Maria Ángeles; San Miguel, Marta; Vázquez, Maria; Castro, Margarita; Ferrer, Isaac; Navarrete, Rosa; Desviat, Lourdes Ruiz; Lapunzina, Pablo; Ugarte, Magdalena; Pérez-Cerdá, Celia

2013-02-01

Pyridoxine-dependent epilepsy seizure (PDE; OMIM 266100) is a disorder associated with severe seizures that can be controlled pharmacologically with pyridoxine. In the majority of patients with PDE, the disorder is caused by the deficient activity of the enzyme α-aminoadipic semialdehyde dehydrogenase (antiquitin protein), which is encoded by the ALDH7A1 gene. The aim of this work was the clinical, biochemical, and genetic analysis of 12 unrelated patients, mostly from Spain, in an attempt to provide further valuable data regarding the wide clinical, biochemical, and genetic spectrum of the disease. The disease was confirmed based on the presence of α-aminoadipic semialdehyde (α-AASA) in urine measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and pipecolic acid (PA) in plasma and/or cerebrospinal fluid (CSF) measured by high performance liquid chromatography (HPLC)/MS/MS and by sequencing analysis of messenger RNA (mRNA) and genomic DNA of ALDH7A1. Most of the patients had seizures in the neonatal period, but they responded to vitamin B6 administration. Three patients developed late-onset seizures, and most patients showed mild-to-moderate postnatal developmental delay. All patients had elevated PA and α-AASA levels, even those who had undergone pyridoxine treatment for several years. The clinical spectrum of our patients is not limited to seizures but many of them show associated neurologic dysfunctions such as muscle tone alterations, irritability, and psychomotor retardation. The mutational spectrum of the present patients included 12 mutations, five already reported (c.500A>G, c.919C>T, c.1429G>C c.1217_1218delAT, and c.1482-1G>T) and seven novel sequence changes (c.75C>T, c.319G>T, c.554_555delAA, c.757C>T, c.787 + 1G>T, c.1474T>C, c.1093-?_1620+?). Only one mutation, p.G477R (c.1429G>C), was recurrent; this was detected in four different alleles. Transcriptional profile analysis of one patient's lymphoblasts and ex vivo splicing analysis showed the silent nucleotide change c.75C>T to be a novel splicing mutation creating a new donor splice site inside exon 1. Antisense therapy of the aberrant mRNA splicing in a lymphoblast cell line harboring mutation c.75C>T was successful. The present results broaden our knowledge of PDE, provide information regarding the genetic background of PDE in Spain, afford data of use when making molecular-based prenatal diagnosis, and provide a cellular proof-of concept for antisense therapy application. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Inhibition of adenosine metabolism induces changes in post-ictal depression, respiration, and mortality in genetically epilepsy prone rats.

PubMed

Kommajosyula, Srinivasa P; Randall, Marcus E; Faingold, Carl L

2016-01-01

A major cause of mortality in epilepsy patients is sudden unexpected death in epilepsy (SUDEP). Post-ictal respiratory dysfunction following generalized convulsive seizures is most commonly observed in witnessed cases of human SUDEP. DBA mouse models of SUDEP are induced by audiogenic seizures (AGSz) and show high incidences of seizure-induced death due to respiratory depression. The relatively low incidence of human SUDEP suggests that it may be useful to examine seizure-associated death in an AGSz model that rarely exhibits sudden death, such as genetically epilepsy-prone rats (GEPR-9s). Adenosine is released extensively during seizures and depresses respiration, which may contribute to seizure-induced death. The present study examined the effects of inhibiting adenosine metabolism on the durations of post-ictal depression (PID) and respiratory distress (RD), changes in blood oxygen saturation (% SpO2), and the incidence of post-seizure mortality in GEPR-9s. Systemic administration of adenosine metabolism inhibitors, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA, 30 mg/kg) with 5-Iodotubericidin (5-ITU, 3mg/kg) in GEPR-9s resulted in significant changes in the duration of AGSz-induced PID as compared to vehicle in both genders. These agents also significantly increased the duration of post-seizure RD and significantly decreased the mean% SpO2 after AGSz, as compared to vehicle but only in females. Subsequently, we observed that the incidences of death in both genders 12-48 h post-seizure were significantly greater in drug vs. vehicle treatment. The incidence of death in females was also significantly higher than in males, which is consistent with the elevated seizure sensitivity of female GEPR-9s developmentally. These results support a potentially important role of elevated adenosine levels following generalized seizures in the increased incidence of death in GEPR-9s induced by adenosine metabolism inhibitors. These findings may also be relevant to human SUDEP, in light of the elevated adenosine levels that occur post-ictally in humans and its respiratory depressant actions. Copyright © 2015 Elsevier B.V. All rights reserved.

Norms for developmental milestones using VABS-II and association with anthropometric measures among apparently healthy urban Indian preschool children.

PubMed

Selvam, Sumithra; Thomas, Tinku; Shetty, Priya; Zhu, Jianjun; Raman, Vijaya; Khanna, Deepti; Mehra, Ruchika; Kurpad, Anura V; Srinivasan, Krishnamachari

2016-12-01

Assessment of developmental milestones based on locally developed norms is critical for accurate estimate of overall development of a child's cognitive, behavioral, social, and emotional development. A cross-sectional study was done to develop age specific norms for developmental milestones using Vineland Adaptive Behavior Scales (VABS-II) (Sparrow, Cicchetti, & Balla, 2005) for apparently healthy children from 2 to 5 years from urban Bangalore, India, and to examine its association with anthropometric measures. Mothers (or caregivers) of 412 children participated in the study. Age-specific norms using inferential norming method and adaptive levels for all domains and subdomains were derived. Low adaptive level, also called delayed developmental milestone, was observed in 2.3% of the children, specifically 2.7% in motor and daily living skills and 2.4% in communication skills. When these children were assessed on the existing U.S. norms, there was a significant overestimation of delayed development in socialization and motor skills, whereas delay in communication and daily living skills were underestimated (all p < .01). Multiple linear regression revealed that stunted and underweight children had significantly lower developmental scores for communication and motor skills compared with normal children (β coefficient ranges from 2.6-5.3; all p < .01). In the absence of Indian normative data for VABS-II in preschool children, the prevalence of developmental delay could either be under- or overestimated using Western norms. Thus, locally referenced norms are critical for reliable assessments of development in children. Stunted and underweight children are more likely to have poorer developmental scores compared with healthy children. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

A prospective study of response to name in infants at risk for autism.

PubMed

Nadig, Aparna S; Ozonoff, Sally; Young, Gregory S; Rozga, Agata; Sigman, Marian; Rogers, Sally J

2007-04-01

To assess the sensitivity and specificity of decreased response to name at age 12 months as a screen for autism spectrum disorders (ASD) and other developmental delays. Prospective, longitudinal design studying infants at risk for ASD. Research laboratory at university medical center. Infants at risk for autism (55 six-month-olds, 101 twelve-month-olds) and a control group at no known risk (43 six-month-olds, 46 twelve-month-olds). To date, 46 at-risk infants and 25 control infants have been followed up to 24 months. Intervention Experimental task eliciting response-to-name behavior. Autism Diagnostic Observation Schedule, Mullen Scales of Early Learning. At age 6 months, there was a nonsignificant trend for control infants to require a fewer number of calls to respond to name than infants at risk for autism. At age 12 months, 100% of infants in the control group "passed," responding on the first or second name call, while 86% in the at-risk group did. Three fourths of children who failed the task were identified with developmental problems at age 24 months. Specificity of failing to respond to name was 0.89 for ASD and 0.94 for any developmental delay. Sensitivity was 0.50 for ASD and 0.39 for any developmental delay. Failure to respond to name by age 12 months is highly suggestive of developmental abnormality but does not identify all children at risk for developmental problems. Lack of responding to name is not universal among infants later diagnosed with ASD and/or other developmental delays. Poor response to name may be a trait of the broader autism phenotype in infancy.

Accelerated long-term forgetting in children with idiopathic generalized epilepsy.

PubMed

Gascoigne, Michael B; Barton, Belinda; Webster, Richard; Gill, Deepak; Antony, Jayne; Lah, Suncica Sunny

2012-12-01

The rapid forgetting of information over long (but not short) delays (accelerated long-term forgetting [ALF]) has been associated with temporal lobe epilepsy but not idiopathic generalized epilepsy (IGE). Long-term memory formation (consolidation) is thought to demand an interaction between medial temporal and neocortical networks, which could be disrupted by epilepsy/seizures themselves. The present study investigates whether ALF is present in children with IGE and whether it relates to epilepsy severity. Sixty-one children (20 with IGE and 41 healthy controls [HC]) of comparable age, sex, and parental socioeconomic status completed neuropsychological tests, including a measure of verbal learning and recall after, short (30-min) and long (7-day) delays, and recognition. Epilepsy severity was rated by treating neurologists. A two-way repeated measures analysis of covariance (ANCOVA) found a significant Group x Delay interaction; the children with IGE recalled (and recognized) significantly fewer words after a long, but not short (2- and 30-min) delay relative to the HC children. Moreover, greater epilepsy severity was associated with poorer recognition. This study demonstrates, to our knowledge for the first time, that children with IGE present with ALF, which is related to epilepsy severity. These findings support the notion that epilepsy/seizures themselves may disrupt long-term memory consolidation, which interferes with day-to-day functioning of children with IGE. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Infections, inflammation and epilepsy

PubMed Central

Vezzani, Annamaria; Fujinami, Robert S.; White, H. Steve; Preux, Pierre-Marie; Blümcke, Ingmar; Sander, Josemir W.; Löscher, Wolfgang

2016-01-01

Epilepsy is the tendency to have unprovoked epileptic seizures. Anything causing structural or functional derangement of brain physiology may lead to seizures, and different conditions may express themselves solely by recurrent seizures and thus be labelled “epilepsy.” Worldwide, epilepsy is the most common serious neurological condition. The range of risk factors for the development of epilepsy varies with age and geographic location. Congenital, developmental and genetic conditions are mostly associated with the development of epilepsy in childhood, adolescence and early adulthood. Head trauma, infections of the central nervous system (CNS) and tumours may occur at any age and may lead to the development of epilepsy. Infections of the CNS are a major risk factor for epilepsy. The reported risk of unprovoked seizures in population-based cohorts of survivors of CNS infections from developed countries is between 6.8 and 8.3 %, and is much higher in resource-poor countries. In this review, the various viral, bacterial, fungal and parasitic infectious diseases of the CNS which result in seizures and epilepsy are discussed. The pathogenesis of epilepsy due to brain infections, as well as the role of experimental models to study mechanisms of epileptogenesis induced by infectious agents, is reviewed. The sterile (non-infectious) inflammatory response that occurs following brain insults is also discussed, as well as its overlap with inflammation due to infections, and the potential role in epileptogenesis. Furthermore, autoimmune encephalitis as a cause of seizures is reviewed. Potential strategies to prevent epilepsy resulting from brain infections and non-infectious inflammation are also considered. PMID:26423537

"Endovascular embolic hemispherectomy": a strategy for the initial management of catastrophic holohemispheric epilepsy in the neonate.

PubMed

Oluigbo, Chima; Pearl, Monica S; Tsuchida, Tammy N; Chang, Taeun; Ho, Cheng-Ying; Gaillard, William D

2017-03-01

Conflicting challenges abound in the management of the newborn with intractable epilepsy related to hemimegalencephaly. Early hemispherectomy to stop seizures and prevent deleterious consequences to future neurocognitive development must be weighed against the technical and anesthetic challenges of performing major hemispheric surgery in the neonate. We hereby present our experience with two neonates with hemimegalencephaly and intractable seizures who were managed using a strategy of initial minimally invasive embolization of the cerebral blood supply to the involved hemisphere. Immediate significant seizure control was achieved after embolization of the cerebral blood supply to the involved hemisphere followed by delayed ipsilateral hemispheric resection at a later optimal age. The considerations and challenges encountered in the course of the management of these patients are discussed, and a literature review is presented.

Neuropathological Comparison of Adult Onset and Juvenile Huntington's Disease with Cerebellar Atrophy: A Report of a Father and Son.

PubMed

Latimer, Caitlin S; Flanagan, Margaret E; Cimino, Patrick J; Jayadev, Suman; Davis, Marie; Hoffer, Zachary S; Montine, Thomas J; Gonzalez-Cuyar, Luis F; Bird, Thomas D; Keene, C Dirk

2017-01-01

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a trinucleotide (CAG) repeat expansion in huntingtin (HTT) on chromosome 4. Anticipation can cause longer repeat expansions in children of HD patients. Juvenile Huntington's disease (JHD), defined as HD arising before age 20, accounts for 5-10% of HD cases, with cases arising in the first decade accounting for approximately 1%. Clinically, JHD differs from the predominately choreiform adult onset Huntington's disease (AOHD) with variable presentations, including symptoms such as myoclonus, seizures, Parkinsonism, and cognitive decline. The neuropathologic changes of AOHD are well characterized, but there are fewer reports that describe the neuropathology of JHD. Here we report a case of a six-year-old boy with paternally-inherited JHD caused by 169 CAG trinucleotide repeats who presented at age four with developmental delay, dysarthria, and seizures before dying at age 6. The boy's clinical presentation and neuropathological findings are directly compared to those of his father, who presented with AOHD and 54 repeats. A full autopsy was performed for the JHD case and a brain-only autopsy was performed for the AOHD case. Histochemically- and immunohistochemically-stained slides were prepared from formalin-fixed, paraffin-embedded tissue sections. Both cases had neuropathology corresponding to Vonsattel grade 3. The boy also had cerebellar atrophy with huntingtin-positive inclusions in the cerebellum, findings not present in the father. Autopsies of father and son provide a unique opportunity to compare and contrast the neuropathologic findings of juvenile and adult onset HD while also providing the first immunohistochemical evidence of cerebellar involvement in JHD. Additionally this is the first known report to include findings from peripheral tissue in a case of JHD.

Neurological Outcomes After Presumed Childhood Encephalitis.

PubMed

Rismanchi, Neggy; Gold, Jeffrey J; Sattar, Shifteh; Glaser, Carol; Sheriff, Heather; Proudfoot, James; Mower, Andrew; Nespeca, Mark; Crawford, John R; Wang, Sonya G

2015-09-01

To evaluate factors during acute presumed childhood encephalitis that are associated with development of long-term neurological sequelae. A total of 217 patients from Rady Children's Hospital San Diego with suspected encephalitis who met criteria for the California Encephalitis Project were identified. A cohort of 99 patients (40 females, 59 males, age 2 months-17 years) without preexisting neurological conditions, including prior seizures or abnormal brain magnetic resonance imaging scans was studied. Mean duration of follow-up was 29 months. Factors that had a relationship with the development of neurological sequelae (defined as developmental delay, learning difficulties, behavioral problems, or focal neurological findings) after acute encephalitis were identified. Neurological sequelae at follow-up was associated with younger age (6.56 versus 9.22 years) at presentation (P = 0.04) as well as an initial presenting sign of seizure (P = 0.03). Duration of hospital stay (median of 7 versus 15.5 days; P = 0.02) was associated with neurological sequelae. Of the patients with neurological sequelae, a longer hospital stay was associated with patients of an older age (P = 0.04). Abnormalities on neuroimaging (P = 1.00) or spinal fluid analysis (P = 1.00) were not uniquely associated with neurological sequelae. Children who were readmitted after their acute illness (P = 0.04) were more likely to develop neurological sequelae. There was a strong relationship between the patients who later developed epilepsy and those who developed neurological sequelae (P = 0.02). Limited data are available on the long-term neurological outcomes of childhood encephalitis. Almost half of our patients were found to have neurological sequelae at follow-up, indicating the importance of earlier therapies to improve neurological outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

[Fulminant liver failure in a patient on carbamazepine and levetiracetam treatment associated with status epilepticus].

PubMed

Skopp, Gisela; Schmitt, Horst Peter; Pedal, Ingo

2006-01-01

A 22-year-old female with a history of developmental delay and seizures successfully treated with carbamazepine and levetiracetam developed fulminant hepatic failure and subsequently died. She had been admitted to the hospital following secondary generalized seizures of 35 min duration. A circulatory shock as well as intoxication was taken into consideration during the clinical course. Autopsy failed to reveal a macroscopically discernible cause of death. Significant findings on microscopic examination included acute tubular necrosis in the kidneys, pre-existing marked accumulation of neutral lipid within the hepatocytes as well as hyperacute liver damage with evidence of almost complete hepatocyte necrosis. Carbamazepine and levetiracetam were simultaneously determined from blood and tissues such as liver, lungs, muscle and kidneys by LC-MS/MS following addition of lamotrigine as an internal standard and liquid-liquid extraction. Validation data are given for levetiracetam. Both carbamazepine and levetiracetam were present in blood at concentrations within or below the therapeutic range, respectively. Moreover, tissue concentrations suggested long-term administration of anticonvulsant drugs, which is in accordance with the medical history. After excessive drug concentrations could be ruled out, the metabolic consequences of a prolonged carbamazepine therapy to cause severe hepatic injury in the present case are discussed. A mechanism of injury to the hepatocytes may be membrane damage by either an increased production of free radicals and/or a decreased free radical scavenging capacity. Following ischemia with reperfusion and during hyperthermia, large amounts of free radicals are formed. Induction of the mixed oxidase activity during longterm administration of carbamazepine may also increase production of free radicals, leaving the hepatic cell more vulnerable to oxidative injury.

Protein instability, haploinsufficiency, and cortical hyper-excitability underlie STXBP1 encephalopathy

PubMed Central

Kovačević, Jovana; Maroteaux, Gregoire; Schut, Desiree; Loos, Maarten; Dubey, Mohit; Pitsch, Julika; Remmelink, Esther; Koopmans, Bastijn; Crowley, James; Cornelisse, L Niels; Sullivan, Patrick F; Schoch, Susanne; Toonen, Ruud F; Stiedl, Oliver; Verhage, Matthijs

2018-01-01

Abstract De novo heterozygous mutations in STXBP1/Munc18-1 cause early infantile epileptic encephalopathies (EIEE4, OMIM #612164) characterized by infantile epilepsy, developmental delay, intellectual disability, and can include autistic features. We characterized the cellular deficits for an allelic series of seven STXBP1 mutations and developed four mouse models that recapitulate the abnormal EEG activity and cognitive aspects of human STXBP1-encephalopathy. Disease-causing STXBP1 variants supported synaptic transmission to a variable extent on a null background, but had no effect when overexpressed on a heterozygous background. All disease variants had severely decreased protein levels. Together, these cellular studies suggest that impaired protein stability and STXBP1 haploinsufficiency explain STXBP1-encephalopathy and that, therefore, Stxbp1+/− mice provide a valid mouse model. Simultaneous video and EEG recordings revealed that Stxbp1+/− mice with different genomic backgrounds recapitulate the seizure/spasm phenotype observed in humans, characterized by myoclonic jerks and spike-wave discharges that were suppressed by the antiepileptic drug levetiracetam. Mice heterozygous for Stxbp1 in GABAergic neurons only, showed impaired viability, 50% died within 2–3 weeks, and the rest showed stronger epileptic activity. c-Fos staining implicated neocortical areas, but not other brain regions, as the seizure foci. Stxbp1+/− mice showed impaired cognitive performance, hyperactivity and anxiety-like behaviour, without altered social behaviour. Taken together, these data demonstrate the construct, face and predictive validity of Stxbp1+/− mice and point to protein instability, haploinsufficiency and imbalanced excitation in neocortex, as the underlying mechanism of STXBP1-encephalopathy. The mouse models reported here are valid models for development of therapeutic interventions targeting STXBP1-encephalopathy. PMID:29538625

Autosomal dominant transmission of a Goldenhar-like syndrome: Description of a family and report of a sporadic case with a de novo 4p16;8q24.11 translocation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graganm H.N. Jr.; Hixon, H.; Bacino, C.A.

1994-09-01

We report vertical transmission of a Goldenhar-like syndrome, including a father and 5 offspring, with male-to-male transmission and variable features that include hearing loss, ear anomalies (microtia, ear tags/pits), branchial cysts, ocular/periocular dermoids, micrognathia and seizures. We also report an individual with an apparently balanced de novo reciprocal translocation with breakpoints at 4p16 and 8q24.11. This individual has unilateral microtia, an epibulbar dermoid cyst, facial asymmetry with a small chin, and seizures. In addition to these features resembling those seen in the family above, she has multiple exostoses, supraventricular tachycardia, hypoglycemia and mild developmental delays. Based on the overlap inmore » physical findings between this family and the individual with the de novo reciprocal translocation, linkage studies on the family were intiated. Preliminary results exclude linkage to HOX 7 at 4p16.1 but not to 8q. The brancho-oto-renal syndrome has previously been localized to 8q11-8q13, but linkage to this region appears unlikely. Although most cases of Goldenhar syndrome appear to be sporadic, there are a few reports of autosomal dominant inheritance (MIM No. 164210). One such family showed vertical transmission of dermoids, ear anomalies, hearing loss, micrognathia and vertebral anomalies, but no branchial cysts. Another family showed sensorineural deafness, preauricular pits, and branchial fistulae, and other families reveal ear anomalies, branchial fistulas, and hearing loss. These latter families appear to lack ocular/periocular dermoids, and appear to be affected by a different disorder (MIM No. 125100). Further clinical delineation of such families, combined with genetic linkage analysis, should help to sort out this heterogeneity.« less

Epilepsy and mental retardation limited to females with PCDH19 mutations can present de novo or in single generation families.

PubMed

Hynes, Kim; Tarpey, Patrick; Dibbens, Leanne M; Bayly, Marta A; Berkovic, Samuel F; Smith, Raffaella; Raisi, Zahyia Al; Turner, Samantha J; Brown, Natasha J; Desai, Tarishi D; Haan, Eric; Turner, Gillian; Christodoulou, John; Leonard, Helen; Gill, Deepak; Stratton, Michael R; Gecz, Jozef; Scheffer, Ingrid E

2010-03-01

Epilepsy and mental retardation limited to females (EFMR) is an intriguing X-linked disorder affecting heterozygous females and sparing hemizygous males. Mutations in the protocadherin 19 (PCDH19) gene have been identified in seven unrelated families with EFMR. Here, we assessed the frequency of PCDH19 mutations in individuals with clinical features which overlap those of EFMR. We analysed 185 females from three cohorts: 42 with Rett syndrome who were negative for MECP2 and CDKL5 mutations, 57 with autism spectrum disorders, and 86 with epilepsy with or without intellectual disability. No mutations were identified in the Rett syndrome and autism spectrum disorders cohorts suggesting that despite sharing similar clinical characteristics with EFMR, PCDH19 mutations are not generally associated with these disorders. Among the 86 females with epilepsy (of whom 51 had seizure onset before 3 years), with or without intellectual disability, we identified two (2.3%) missense changes. One (c.1671C-->G, p.N557K), reported previously without clinical data, was found in two affected sisters, the first EFMR family without a multigenerational family history of affected females. The second, reported here, is a novel de novo missense change identified in a sporadic female. The change, p.S276P, is predicted to result in functional disturbance of PCDH19 as it affects a highly conserved residue adjacent to the adhesion interface of EC3 of PCDH19. This de novo PCDH19 mutation in a sporadic female highlights that mutational analysis should be considered in isolated instances of girls with infantile onset seizures and developmental delay, in addition to those with the characteristic family history of EFMR.

Novel loss-of-function variants in DIAPH1 associated with syndromic microcephaly, blindness, and early onset seizures.

PubMed

Al-Maawali, Almundher; Barry, Brenda J; Rajab, Anna; El-Quessny, Malak; Seman, Ann; Coury, Stephanie Newton; Barkovich, A James; Yang, Edward; Walsh, Christopher A; Mochida, Ganeshwaran H; Stoler, Joan M

2016-02-01

Exome sequencing identified homozygous loss-of-function variants in DIAPH1 (c.2769delT; p.F923fs and c.3145C>T; p.R1049X) in four affected individuals from two unrelated consanguineous families. The affected individuals in our report were diagnosed with postnatal microcephaly, early-onset epilepsy, severe vision impairment, and pulmonary symptoms including bronchiectasis and recurrent respiratory infections. A heterozygous DIAPH1 mutation was originally reported in one family with autosomal dominant deafness. Recently, however, a homozygous nonsense DIAPH1 mutation (c.2332C4T; p.Q778X) was reported in five siblings in a single family affected by microcephaly, blindness, early onset seizures, developmental delay, and bronchiectasis. The role of DIAPH1 was supported using parametric linkage analysis, RNA and protein studies in their patients' cell lines and further studies in human neural progenitors cells and a diap1 knockout mouse. In this report, the proband was initially brought to medical attention for profound metopic synostosis. Additional concerns arose when his head circumference did not increase after surgical release at 5 months of age and he was diagnosed with microcephaly and epilepsy at 6 months of age. Clinical exome analysis identified a homozygous DIAPH1 mutation. Another homozygous DIAPH1 mutation was identified in the research exome analysis of a second family with three siblings presenting with a similar phenotype. Importantly, no hearing impairment is reported in the homozygous affected individuals or in the heterozygous carrier parents in any of the families demonstrating the autosomal recessive microcephaly phenotype. These additional families provide further evidence of the likely causal relationship between DIAPH1 mutations and a neurodevelopmental disorder. © 2016 Wiley Periodicals, Inc.

Genotype–phenotype correlations in neonatal epilepsies caused by mutations in the voltage sensor of Kv7.2 potassium channel subunits

PubMed Central

Miceli, Francesco; Soldovieri, Maria Virginia; Ambrosino, Paolo; Barrese, Vincenzo; Migliore, Michele; Cilio, Maria Roberta; Taglialatela, Maurizio

2013-01-01

Mutations in the KV7.2 gene encoding for voltage-dependent K+ channel subunits cause neonatal epilepsies with wide phenotypic heterogeneity. Two mutations affecting the same positively charged residue in the S4 domain of KV7.2 have been found in children affected with benign familial neonatal seizures (R213W mutation) or with neonatal epileptic encephalopathy with severe pharmacoresistant seizures and neurocognitive delay, suppression-burst pattern at EEG, and distinct neuroradiological features (R213Q mutation). To examine the molecular basis for this strikingly different phenotype, we studied the functional characteristics of mutant channels by using electrophysiological techniques, computational modeling, and homology modeling. Functional studies revealed that, in homomeric or heteromeric configuration with KV7.2 and/or KV7.3 subunits, both mutations markedly destabilized the open state, causing a dramatic decrease in channel voltage sensitivity. These functional changes were (i) more pronounced for channels incorporating R213Q- than R213W-carrying KV7.2 subunits; (ii) proportional to the number of mutant subunits incorporated; and (iii) fully restored by the neuronal Kv7 activator retigabine. Homology modeling confirmed a critical role for the R213 residue in stabilizing the activated voltage sensor configuration. Modeling experiments in CA1 hippocampal pyramidal cells revealed that both mutations increased cell firing frequency, with the R213Q mutation prompting more dramatic functional changes compared with the R213W mutation. These results suggest that the clinical disease severity may be related to the extent of the mutation-induced functional K+ channel impairment, and set the preclinical basis for the potential use of Kv7 openers as a targeted anticonvulsant therapy to improve developmental outcome in neonates with KV7.2 encephalopathy. PMID:23440208

Using Animation in Microsoft PowerPoint to Enhance Engagement and Learning in Young Learners with Developmental Delay

ERIC Educational Resources Information Center

Parette, Howard P., Jr.; Hourcade, Jack; Blum, Craig

2011-01-01

Over the past decade, a wide array of instructional technology applications have found their way into early intervention settings. Of particular importance to young learners who evidence developmental delays or are at risk for school failure are those technologies with the potential to more effectively teach basic emergent literacy skills: (1)…

Predictors of Depressive Symptoms in Primary Caregivers of Young Children with or at Risk for Developmental Delay

ERIC Educational Resources Information Center

Feldman, M.; McDonald, L.; Serbin, L.; Stack, D.; Secco, M. L.; Yu, C. T.

2007-01-01

Background: Despite extensive research with families raising children with or at risk for developmental delay (DD), it is not clear whether primary caregivers of these children are at increased risk for depressive symptoms. Discrepant findings in the literature may be owing to heterogeneity of child problems. More research is needed on child,…

Teaching Language Skills to Preschool Students with Developmental Delays and Autism Spectrum Disorder Using Language for Learning

ERIC Educational Resources Information Center

Flores, Margaret M.; Schweck, Kelly B.; Hinton, Vanessa

2016-01-01

Language intervention using Direct Instruction (DI) has shown positive results. There is a growing body of investigation of Language for Learning (LL), a DI program, on the performance of students with autism spectrum disorders (ASD) and students with developmental delays (DD). There is need for replication and extension of research to include…

A Digest and Comparative Analysis of Major Federal Programs Affecting Infants and Toddlers with Handicaps and Their Families.

ERIC Educational Resources Information Center

O'Reilly, Fran E.; And Others

This study analyzes major federal programs designed to provide services to children, from birth through age 2, who have developmental delays or a high probability of developmental delays, and their families. Programs were selected based on their provision of education or health-related services to infants and toddlers with handicaps and their…

Longitudinal Assessment of Stereotypic, Proto-Injurious, and Self-Injurious Behavior Exhibited by Young Children with Developmental Delays

ERIC Educational Resources Information Center

Richman, David M.; Lindauer, Steven E.

2005-01-01

Twelve children (CA, 12 to 32 months) with developmental delay were observed in their homes during monthly analogue functional analysis probes to document patterns of emerging self-injurious behavior. Two patterns of emerging self-injury were observed for 5 participants: (a) The topography and functional analysis pattern remained the same, but the…

The Administrative Population Report on Children with Developmental Delays in Taiwan, 2003 through 2007

ERIC Educational Resources Information Center

Lin, Jin-Ding; Yen, Chia-Feng; Wu, Jia-Ling; Kang, Shih-Wan

2009-01-01

This paper was a population study with developmental delays and it included an examination of the trends the overtime change trend and reported channels of this group of people in Taiwan. We analyzed data for the present study mainly from the Department of Statistics, Ministry of the Interiors, Taipei, Taiwan: "Number of early intervention…

State and Jurisdictional Eligibility Definitions for Infants and Toddlers with Disabilities under IDEA. Nectas Notes, Number 5. Revised.

ERIC Educational Resources Information Center

Shackelford, Jo

Under Part C of the Individuals with Disabilities Education Act (IDEA), participating states and jurisdictions must provide services to children who are either experiencing developmental delays, or who have a diagnosed condition that carries with it a high risk of developmental delay. Eligibility criteria used by the states influence the numbers…

The Effects of Imitation Instruction Using a Mirror on the Emergence of Duplicative Responses by Preschool Students Diagnosed with Developmental Delays

ERIC Educational Resources Information Center

Moreno, Jalene Donica

2012-01-01

Using pre-and post-intervention non-concurrent multiple probe designs across participants, I conducted 2 experiments that tested the effects of imitation instruction using a mirror on the emergence of both basic and advanced forms of generalized imitation (GI) involving physical actions with preschool students diagnosed with developmental delays.…

Global Perspective on Early Diagnosis and Intervention for Children with Developmental Delays and Disabilities

ERIC Educational Resources Information Center

Scherzer, Alfred L.; Chhagan, Meera; Kauchali, Shuaib; Susser, Ezra

2012-01-01

Low- and middle-income countries are experiencing a significant reduction in mortality of children under 5 years of age. This reduction is bringing in its wake large numbers of surviving children with developmental delays and disabilities. Very little attention has been paid to these children, most of whom receive minimal or no support. Thus,…

State and Jurisdictional Eligibility Definitions for Infants and Toddlers with Disabilities under IDEA. NECTAC Notes Issue No. 14

ERIC Educational Resources Information Center

Shackelford, Jo

2004-01-01

Under Part C of the Individuals with Disabilities Education Act (IDEA), participating states and jurisdictions must provide services to children who are either experiencing developmental delays, or who have a diagnosed mental or physical condition that has a high probability of resulting in developmental delay. Additionally, states may choose to…

Mindfulness-Based Stress Reduction for Parents of Young Children with Developmental Delays: Implications for Parental Mental Health and Child Behavior Problems

ERIC Educational Resources Information Center

Neece, Cameron L.

2014-01-01

Background: Parents of children with developmental delays (DD) typically report elevated levels of parental stress compared with parents of typically developing children. Children with DD are also at high risk for exhibiting significant behaviour problems. Parental stress has been shown to impact the development of these behaviour problems;…

Comparing Service Delivery Models for Children with Developmental Delays in Canada: Adaptive and Maladaptive Behaviours, Parental Perceptions of Stress and of Care

ERIC Educational Resources Information Center

Sladeczek, Ingrid E.; Fontil, Laura; Miodrag, Nancy; Karagiannakis, Anastasia; Amar, Daniel; Amos, Janet

2017-01-01

This study compares two service delivery models (community-based and centre-based), examining them in light of children's adaptive and maladaptive behaviours, and parental perceptions of stress and of care. More specifically, parents of 96 children with developmental delays assessed their children's adaptive and maladaptive behaviours and rated…

Review of Recent Research Using Constant Time Delay to Teach Chained Tasks to Persons with Developmental Disabilities

ERIC Educational Resources Information Center

Dogoe, Maud; Banda, Devender R.

2009-01-01

We reviewed twelve studies that used the constant time delay (CTD) procedure to teach chained tasks to individuals with developmental disabilities from years 1996-2006. Variables analyzed include types of tasks that have been taught with the procedure, how effective CTD has been in teaching participants, and whether researchers have investigated…

Implementing Visually Cued Imitation Training with Children with Autism Spectrum Disorders and Developmental Delays

ERIC Educational Resources Information Center

Ganz, Jennifer B.; Bourgeois, Bethany C.; Flores, Margaret M.; Campos, B. Adriana

2008-01-01

Clearly, imitation is linked to a variety of skill areas. As a result, children with autism and developmental delays are less likely than their typical peers to perform well in many areas of development, including play and speech. The purpose of this study was to determine if a simple, teacher-friendly strategy could be implemented that would…

Modeling Skills, Signs and Lettering for Children with Down Syndrome, Autism and Other Severe Developmental Delays by Video Instruction in Classroom Setting

ERIC Educational Resources Information Center

Biederman, G. B.; Freedman, B.

2007-01-01

This paper addresses optimal strategies in teaching essential life and communication skills to children with Down syndrome, autism and other developmental delays. Evidence from the literature concerning the relative efficacy of hand-over-hand (self-modeling) in contrast to passive observational teaching techniques (e.g., video modeling) shows the…

Father's role in parent training for children with developmental delay.

PubMed

Bagner, Daniel M

2013-08-01

The current pilot study was a quasi-experimental examination of the impact of father involvement in parent training among 44 families with a young child who presented with elevated externalizing behavior problems and developmental delay. All families were offered to receive Parent-Child Interaction Therapy (PCIT), an evidence-based parent-training intervention, at a hospital-based outpatient clinic. Single-mother families were significantly more likely to drop out of treatment than two-parent families. Of the families that completed treatment, children from families in which a father participated in treatment had lower levels of parent-reported externalizing behavior problems than children from single-mother families and children from two-parent families in which the father did not participate in treatment. Additionally, children from father-involved families were significantly more compliant during a cleanup task than children from single-mother families following treatment. The current study is consistent with the limited research examining father involvement in parent training and extends the findings to children with developmental delay. These findings highlight the importance of involving fathers in parent training, particularly when working with children with developmental delay. © 2013 American Psychological Association

Developmental PCB Exposure Increases Audiogenic Seizures and Decreases Glutamic Acid Decarboxylase in the Inferior Colliculus

PubMed Central

Bandara, Suren B.; Eubig, Paul A.; Sadowski, Renee N.; Schantz, Susan L.

2016-01-01

Previously, we observed that developmental polychlorinated biphenyl (PCB) exposure resulted in an increase in audiogenic seizures (AGSs) in rats. However, the rats were exposed to loud noise in adulthood, and were not tested for AGS until after 1 year of age, either of which could have interacted with early PCB exposure to increase AGS susceptibility. This study assessed susceptibility to AGS in young adult rats following developmental PCB exposure alone (without loud noise exposure) and investigated whether there was a decrease in GABA inhibitory neurotransmission in the inferior colliculus (IC) that could potentially explain this effect. Female Long-Evans rats were dosed orally with 0 or 6 mg/kg/day of an environmentally relevant PCB mixture from 28 days prior to breeding until the pups were weaned at postnatal day 21. One male-female pair from each litter was retained for the AGS study whilst another was retained for Western blot analysis of glutamic acid decarboxylase (GAD) and GABAAα1 receptor in the IC, the site in the auditory midbrain where AGS are initiated. There was a significant increase in the number and severity of AGSs in the PCB groups, with females somewhat more affected than males. GAD65 was decreased but there was no change in GAD67 or GABAAα1 in the IC indicating decreased inhibitory regulation in the PCB group. These results confirm that developmental PCB exposure alone is sufficient to increase susceptibility to AGS, and provide the first evidence for a possible mechanism of action at the level of the IC. PMID:26543103

The molecular and phenotypic spectrum of IQSEC2-related epilepsy.

PubMed

Zerem, Ayelet; Haginoya, Kazuhiro; Lev, Dorit; Blumkin, Lubov; Kivity, Sara; Linder, Ilan; Shoubridge, Cheryl; Palmer, Elizabeth Emma; Field, Michael; Boyle, Jackie; Chitayat, David; Gaillard, William D; Kossoff, Eric H; Willems, Marjolaine; Geneviève, David; Tran-Mau-Them, Frederic; Epstein, Orna; Heyman, Eli; Dugan, Sarah; Masurel-Paulet, Alice; Piton, Ame'lie; Kleefstra, Tjitske; Pfundt, Rolph; Sato, Ryo; Tzschach, Andreas; Matsumoto, Naomichi; Saitsu, Hirotomo; Leshinsky-Silver, Esther; Lerman-Sagie, Tally

2016-11-01

IQSEC2 is an X-linked gene associated with intellectual disability (ID) and epilepsy. Herein we characterize the epilepsy/epileptic encephalopathy of patients with IQSEC2 pathogenic variants. Forty-eight patients with IQSEC2 variants were identified worldwide through Medline search. Two patients were recruited from our early onset epileptic encephalopathy cohort and one patient from personal communication. The 18 patients who have epilepsy in addition to ID are the subject of this study. Information regarding the 18 patients was ascertained by questionnaire provided to the treating clinicians. Six affected individuals had an inherited IQSEC2 variant and 12 had a de novo one (male-to-female ratio, 12:6). The pathogenic variant types were as follows: missense (8), nonsense (5), frameshift (1), intragenic duplications (2), translocation (1), and insertion (1). An epileptic encephalopathy was diagnosed in 9 (50%) of 18 patients. Seizure onset ranged from 8 months to 4 years; seizure types included spasms, atonic, myoclonic, tonic, absence, focal seizures, and generalized tonic-clonic (GTC) seizures. The electroclinical syndromes could be defined in five patients: late-onset epileptic spasms (three) and Lennox-Gastaut or Lennox-Gastaut-like syndrome (two). Seizures were pharmacoresistant in all affected individuals with epileptic encephalopathy. The epilepsy in the other nine patients had a variable age at onset from infancy to 18 years; seizure types included GTC and absence seizures in the hereditary cases and GTC and focal seizures in de novo cases. Seizures were responsive to medical treatment in most cases. All 18 patients had moderate to profound intellectual disability. Developmental regression, autistic features, hypotonia, strabismus, and white matter changes on brain magnetic resonance imaging (MRI) were prominent features. The phenotypic spectrum of IQSEC2 disorders includes epilepsy and epileptic encephalopathy. Epileptic encephalopathy is a main clinical feature in sporadic cases. IQSEC2 should be evaluated in both male and female patients with an epileptic encephalopathy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Recent Advances in Developmental Pediatrics Related to Achievement and Social Behavior.

ERIC Educational Resources Information Center

Mathews, Wendy S.; Barabas, Gabor

1985-01-01

Recent advances related to the achievement and school behavior in children with tic syndromes, seizure disorders, and minor physical anomolies are discussed. The role of the school psychologist as liaison between the pupil's teacher, family, and physician is described, as well as his or her role with the children themselves. (Author/EGS)

The Effects of Antiepileptic Medications on the Social Skills of Individuals with Mental Retardation

ERIC Educational Resources Information Center

Matson, Johnny L.; Luke, Melissa A.; Mayville, Stephen B.

2004-01-01

Prevalence rates of epilepsy are much higher among persons with developmental disabilities compared to the general population. Anticonvulsant medication is the most common method of treating seizure disorders. Many of these antiepileptic medications (AEDs) are associated with various side effects, which may have detrimental effects on the social…

[Multiplex Ligation - dependent Probe Amplification (MLPA) as a screening test in children with developmental defects and intellectual disability of unknown etiology].

PubMed

Laczmańska, Izabela; Jakubiak, Aleksandra; Slęzak, Ryszard; Pesz, Karolina; Stembalska, Agnieszka; Laczmański, Lukasz; Sąsiadek, Maria M; Smigiel, Robert

2011-01-01

Developmental delay and intellectual disability are significant medical and social problems which concern 1-3% of population. The etiology remains unknown in over half of the cases. To evaluate the efficiency of MLPA (Multiplex Ligation-dependent Probe Amplification) as a screening test in diagnosis of patients with developmental delay and/or intellectual disability. 313 MLPA tests were performed in 256 patients with developmental delay and/ or intellectual disability with unknown etiology. MLPA test was made after exclusion of genetic disorders possible to diagnose by dysmorphological examination or using specifi c genetic tests. Positive results were confirmed by FISH analysis with appropriate probes. Chromosomal microaberrations were identifi ed in 15 patients (4,8%): deletions of 1p36 in 4 cases, in one case deletion of 22q11.21, 22q13.33, SNRPN1, 4ptel, 6qtel, 7q11.23, 16ptel, 18qtel as well as one ca se of deletion 3ptel/duplication 15qtel; deletion 18qtel/duplication Xqtel, and also duplication 7q11.23. Detail clinical analysis was performed in patients with diagnosed microaberrations in MLPA test. The molecular MLPA test, screening for chromosomal microaberration syndromes, should be performed in each patient with developmental delay and/or intellectual disability of unknown etiology and normal cytogenetic analysis, even if congenital defects and positive familial history do not exist.

From cognitive networks to seizures: Stimulus evoked dynamics in a coupled cortical network

NASA Astrophysics Data System (ADS)

Lee, Jaejin; Ermentrout, Bard; Bodner, Mark

2013-12-01

Epilepsy is one of the most common neuropathologies worldwide. Seizures arising in epilepsy or in seizure disorders are characterized generally by uncontrolled spread of excitation and electrical activity to a limited region or even over the entire cortex. While it is generally accepted that abnormal excessive firing and synchronization of neuron populations lead to seizures, little is known about the precise mechanisms underlying human epileptic seizures, the mechanisms of transitions from normal to paroxysmal activity, or about how seizures spread. Further complication arises in that seizures do not occur with a single type of dynamics but as many different phenotypes and genotypes with a range of patterns, synchronous oscillations, and time courses. The concept of preventing, terminating, or modulating seizures and/or paroxysmal activity through stimulation of brain has also received considerable attention. The ability of such stimulation to prevent or modulate such pathological activity may depend on identifiable parameters. In this work, firing rate networks with inhibitory and excitatory populations were modeled. Network parameters were chosen to model normal working memory behaviors. Two different models of cognitive activity were developed. The first model consists of a single network corresponding to a local area of the brain. The second incorporates two networks connected through sparser recurrent excitatory connectivity with transmission delays ranging from approximately 3 ms within local populations to 15 ms between populations residing in different cortical areas. The effect of excitatory stimulation to activate working memory behavior through selective persistent activation of populations is examined in the models, and the conditions and transition mechanisms through which that selective activation breaks down producing spreading paroxysmal activity and seizure states are characterized. Specifically, we determine critical parameters and architectural changes that produce the different seizure dynamics in the networks. This provides possible mechanisms for seizure generation. Because seizures arise as attractors in a multi-state system, the system may possibly be returned to its baseline state through some particular stimulation. The ability of stimulation to terminate seizure dynamics in the local and distributed models is studied. We systematically examine when this may occur and the form of the stimulation necessary for the range of seizure dynamics. In both the local and distributed network models, termination is possible for all seizure types observed by stimulation possessing some particular configuration of spatial and temporal characteristics.

Developmental Assessment with Young Children: A Systematic Review of Battelle Studies

ERIC Educational Resources Information Center

Cunha, Ana C. B.; Berkovits, Michelle D.; Albuquerque, Karolina A.

2018-01-01

Developmental assessment scales are important tools for determining developmental delays and planning preventive interventions. One broad assessment scale used to evaluate child development is the Battelle Developmental Inventories (BDIs). The BDI-2 has a standardized version in English with good psychometric properties and a translated version in…

Symbolic play of preschoolers with severe communication impairments with autism and other developmental delays: more similarities than differences.

PubMed

Thiemann-Bourque, Kathy S; Brady, Nancy C; Fleming, Kandace K

2012-05-01

Children with autism are often described as having deficient play skills, particularly symbolic play. We compared the play of 35 children with autism to 38 children with other developmental delays. All children were preschool-age and produced less than 20 different words. Results indicated no significant differences across the two groups in their play. Children with autism engaged in more conventional play, that is, putting objects together according to how the toys were constructed (e.g., pieces in a puzzle, lid on a teapot). Results also indicated high correlations between play, language, and cognitive measures. Findings indicate that play relates to language and cognitive levels yet may not discriminate children with autism and children with other developmental delays early in their development.

Symbolic Play of Preschoolers with Severe Communication Impairments with Autism and Other Developmental Delays: More Similarities than Differences

PubMed Central

Brady, Nancy C.; Fleming, Kandace K.

2011-01-01

Children with autism are often described as having deficient play skills, particularly symbolic play. We compared the play of 35 children with autism to 38 children with other developmental delays. All children were preschool-age and produced less than 20 different words. Results indicated no significant differences across the two groups in their play. Children with autism engaged in more conventional play, that is, putting objects together according to how the toys were constructed (e.g., pieces in a puzzle, lid on a teapot). Results also indicated high correlations between play, language, and cognitive measures. Findings indicate that play relates to language and cognitive levels yet may not discriminate children with autism and children with other developmental delays early in their development. PMID:21720725

Developmental delay and connective tissue disorder in four patients sharing a common microdeletion at 6q13-14.

PubMed

Van Esch, Hilde; Rosser, Elisabeth M; Janssens, Sandra; Van Ingelghem, Ingrid; Loeys, Bart; Menten, Bjorn

2010-10-01

Interstitial deletions of the long arm of chromosome 6 are rare, and most reported cases represent large, cytogenetically detectable deletions. The implementation of array comparative genome hybridisation in the diagnostic work-up of patients presenting with congenital disorders, including developmental delay, has enabled identification of many patients with smaller chromosomal imbalances. In this report, the cases are presented of four patients with a de novo interstitial deletion of chromosome 6q13-14, resulting in a common microdeletion of 3.7 Mb. All presented with developmental delay, mild dysmorphism and signs of lax connective tissue. Interestingly, the common deleted region harbours 16 genes, of which COL12A1 is a good candidate for the connective tissue pathology.

Anaesthesia for electroconvulsive therapy - new tricks for old drugs: a systematic review.

PubMed

Stripp, Tobias Kvist; Jorgensen, Martin Balslev; Olsen, Niels Vidiendal

2018-04-01

The objective of this review is to investigate existing literature in order to delineate whether the use of anaesthesia and timing of seizure induction in a new and optimised way may improve the efficacy of electroconvulsive therapy (ECT). PubMed/MEDLINE was searched for existing literature, last search on 24 June 2015. Relevant clinical studies on human subjects involving choice of anaesthetic, ventilation and bispectral index (BIS) monitoring in the ECT setting were considered. The references of relevant studies were likewise considered. Propofol yields the shortest seizures, etomidate and ketamine the longest. Etomidate and ketamine+propofol 1 : 1 seems to yield the seizures with best quality. Seizure quality is improved when induction of ECT is delayed until the effect of the anaesthetic has waned - possibly monitored with BIS values. Manual hyperventilation with 100% O2 may increase the pO2/pCO2-ratio, which may be correlated with better seizure quality. Etomidate or a 1 : 1 ketamine and propofol combination may be the best method to achieve general anaesthesia in the ECT setting. There is a need for large randomised prospective studies comparing the effect of methohexital, thiopental, propofol, ketamine, propofol+ketamine 1 : 1 and etomidate in the ECT treatment of major depressed patients. These studies should investigate safety and side effects, and most importantly have antidepressant efficacy and cognitive side effects as outcome measures instead of seizure quality.

Neonatal isolation delays the developmental decline of long-term depression in the CA1 region of rat hippocampus.

PubMed

Ku, Hsiao-Yun; Huang, Yu-Fei; Chao, Pei-Hsuan; Huang, Chiung-Chun; Hsu, Kuei-Sen

2008-11-01

Activity-dependent alterations of synaptic efficacy or connectivity are essential for the development, signal processing, and learning and memory functions of the nervous system. It was observed that, in particular in the CA1 region of the hippocampus, low-frequency stimulation (LFS) became progressively less effective at inducing long-term depression (LTD) with advancing developmental age. The physiological factors regulating this developmental plasticity change, however, have not yet been elucidated. Here we examined the hypothesis that neonatal isolation (once per day for 1 h from postnatal days 1-7) is able to alter processes underlying the developmental decline of LTD. We confirm that the magnitude of LTD induced by LFS (900 stimuli at 1 Hz) protocol correlates negatively with developmental age and illustrates that neonatal isolation delays this developmental decline via the activation of corticotrophin-releasing factor (CRF) system. Furthermore, this modulation appears to be mediated by an increased transcription of N-methyl-D-aspartate receptor NR2B subunits. We also demonstrate that intracerebroventricular injection of CRF postnatally mimicked the effect of neonatal isolation to increase the expression of NR2B subunits and delayed the developmental decline of LTD, which was specifically blocked by CRF receptor 1 antagonist NBI27914 pretreatment. These results suggest a novel role for CRF in regulating developmental events in the hippocampus and indicate that although maternal deprivation is stressful for neonate, appropriate neonatal isolation can serve to promote an endocrine state that may regulate the gradual developmental change in the induction rules for synaptic plasticity in the hippocampal CA1 region.

Exonic deletions of AUTS2 in Chinese patients with developmental delay and intellectual disability.

PubMed

Fan, Yanjie; Qiu, Wenjuan; Wang, Lili; Gu, Xuefan; Yu, Yongguo

2016-02-01

Genomic rearrangements involving dosage change of genes have been implicated in a range of developmental disorders. Increasing evidences suggest copy number variations (CNVs) of autism susceptibility candidate gene 2 (AUTS2) are associated with a syndromic form of developmental delay and intellectual disability. However, the genetic and clinical profiles involving AUTS2 variations have not been fully characterized in Asian patients yet, and the outcome of treatments has not been reported. Here we report de novo exonic deletions of AUTS2 detected by chromosomal microarray analysis (CMA) in three Chinese children referred to the clinic for developmental delay, including two deletions involving only exon 6 (98.4 and 262 kb, respectively) and one deletion involving the C-terminal of AUTS2 (2147 kb). The phenotypic presentations of these three patients were described and compared with previous cases in literature. In addition, we presented the outcome of hormonal treatment for short stature in one patient. © 2015 Wiley Periodicals, Inc.

Socioeconomic Status Index to Interpret Inequalities in Child Development

PubMed Central

AHMADI DOULABI, Mahbobeh; SAJEDI, Firoozeh; VAMEGHI, Roshanak; MAZAHERI, Mohammad Ali; AKBARZADEH BAGHBAN, Alireza

2017-01-01

Objective There have been contradictory findings on the relationship between Socioeconomic Status (SES) and child development although SES is associated with child development outcomes. The present study intended to define the relationship between SES and child development in Tehran kindergartens, Iran. Materials & Methods This cross-sectional survey studied 1036 children aged 36-60 month, in different kindergartens in Tehran City, Iran, in 2014-2015. The principal factor analysis (PFA) model was employed to construct SES indices. The constructed SES variable was employed as an independent variable in logistic regression model to evaluate its role in developmental delay as a dependent variable. Results The relationship between SES and developmental delay was significant at P=0.003. SES proved to have a significant (P<0.05) impact on developmental delay, both as an independent variable and after controlling risk factors. Conclusion There should be more emphasis on developmental monitoring and appropriate intervention programs for children to give them higher chance of having a more productive life. PMID:28698723

Predictors of receiving therapy among very low birth weight 2-year olds eligible for Part C early intervention in Wisconsin.

PubMed

McManus, Beth Marie; Robert, Stephanie; Albanese, Aggie; Sadek-Badawi, Mona; Palta, Mari

2013-07-11

The Individuals with Disabilities Education Act (Part C) authorizes states to establish systems to provide early intervention services (e.g., therapy) for children at risk, with the incentive of federal financial support. This study examines family and neighborhood characteristics associated with currently utilizing physical, occupational, or speech therapy among very low birthweight (VLBW) 2-year-old children who meet Wisconsin eligibility requirements for early intervention services (EI) due to developmental delay. This cross-sectional analysis used data from the Newborn Lung Project, a regional cohort study of VLBW infants hospitalized in Wisconsin's newborn intensive care units during 2003-2004. We included the 176 children who were age two at follow-up, and met Wisconsin state eligibility requirements for EI based on developmental delay. Exact logistic regression was used to describe child and neighborhood socio-demographic correlates of parent-reported receipt of therapy. Among VLBW children with developmental delay, currently utilizing therapy was higher among children with Medicaid (aOR = 5.3, 95% CI: 1.3, 28.3) and concomitant developmental disability (aOR = 5.2, 95% CI: 2.1, 13.3) and lower for those living in a socially more disadvantaged neighborhood (aOR=0.48, 95% CI: 0.21, 0.98, per tertile). Among a sample of VLBW 2-year olds with developmental delays who are EI-eligible in WI, 4 out of 5 were currently receiving therapy, per parent report. Participation in Medicaid positively influences therapy utilization. Children with developmental difficulties who live in socially disadvantaged neighborhoods are at highest risk for not receiving therapy.

The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultz, M.K.; Wright, L.K.M.; Stone, M.F.

2012-03-15

Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of γ-aminobutyric acid A (GABA{sub A}) receptors. However, seizure activity itself causes the endocytosis of GABA{sub A} receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-D-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20 mg/kg, im) and DZP (10 mg/kg, sc), administered both separately and in combination, at 10, 20 or 30 min followingmore » seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD{sub 50}; 132 μg/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2 mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20–30 min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. -- Highlights: ► Soman (GD) produced seizure activity resulting in neuropathology in rats. ► Tx: caramiphen (CED) and/or diazepam (DZP) @ 10, 20 or 30 min after seizure onset. ► CED/DZP showed superior anticonvulsant and neuroprotective capacity. ► Physostigmine (PHY) was examined as an adjunct post-exposure therapy. ► PHY attenuated GD-induced seizure development, but not seizure duration.« less

Temporal Lobe Epilepsy in Children

PubMed Central

Nickels, Katherine C.; Wong-Kisiel, Lily C.; Moseley, Brian D.; Wirrell, Elaine C.

2012-01-01

The temporal lobe is a common focus for epilepsy. Temporal lobe epilepsy in infants and children differs from the relatively homogeneous syndrome seen in adults in several important clinical and pathological ways. Seizure semiology varies by age, and the ictal EEG pattern may be less clear cut than what is seen in adults. Additionally, the occurrence of intractable seizures in the developing brain may impact neurocognitive function remote from the temporal area. While many children will respond favorably to medical therapy, those with focal imaging abnormalities including cortical dysplasia, hippocampal sclerosis, or low-grade tumors are likely to be intractable. Expedient workup and surgical intervention in these medically intractable cases are needed to maximize long-term developmental outcome. PMID:22957247

Patterns of Early Skill Attainment and Loss in Young Children with Autism

PubMed Central

Thurm, Audrey; Manwaring, Stacy S.; Luckenbaugh, David A.; Lord, Catherine; Swedo, Susan E.

2015-01-01

The purpose of this study was to extend the literature on the ontogeny of autism spectrum disorder (ASD) by examining early attainment and loss of specific sociocommunicative skills in children with autism (AUT; n = 125), pervasive developmental disorder not otherwise specified (PDD-NOS; n = 42), nonspectrum developmental delays (n = 46), and typical development (n = 31). The ages of skill attainment and loss were obtained from a caregiver interview. The findings indicated that children with AUT, PDD-NOS, and developmental delays diverged from typically developing children in attainment of sociocommunicative skills early in the first year of life. Loss of at least one skill was reported in a majority of children with AUT and PDD-NOS. Significant delays in attainment of skills were also reported in children who lost skills. The wide variation in skill attainment and loss reported across children indicates that symptom onset and regression may be best represented continuously, with at least some early delay and loss present for a great majority of children with ASD. PMID:24274034

Patterns of skill attainment and loss in young children with autism.

PubMed

Thurm, Audrey; Manwaring, Stacy S; Luckenbaugh, David A; Lord, Catherine; Swedo, Susan E

2014-02-01

The purpose of this study was to extend the literature on the ontogeny of autism spectrum disorder (ASD) by examining early attainment and loss of specific sociocommunicative skills in children with autism (AUT; n = 125), pervasive developmental disorder not otherwise specified (PDD-NOS; n = 42), nonspectrum developmental delays (n = 46), and typical development (n = 31). The ages of skill attainment and loss were obtained from a caregiver interview. The findings indicated that children with AUT, PDD-NOS, and developmental delays diverged from typically developing children in attainment of sociocommunicative skills early in the first year of life. Loss of at least one skill was reported in a majority of children with AUT and PDD-NOS. Significant delays in attainment of skills were also reported in children who lost skills. The wide variation in skill attainment and loss reported across children indicates that symptom onset and regression may be best represented continuously, with at least some early delay and loss present for a great majority of children with ASD.

Peripheral Innervation in Children with Global Developmental Delay: Biomarker for Risk for Self-Injurious Behavior?

PubMed Central

Symons, Frank J.; Tervo, Raymond C.; Barney, Chantel C.; Damerow, John; Selim, Mona; McAdams, Brian; Foster, Shawn; Crabb, Gwen Wendelschafer; Kennedy, William

2015-01-01

The relation between somatosensory mechanisms and self-injury among children with neurological impairments associated with developmental delay is not well understood. We evaluated the feasibility of procuring skin biopsies to examine epidermal nerve fiber density and reported self-injury. Following informed parental consent, epidermal skin biopsies were obtained from a distal leg site with no pre-existing skin damage from 11 children with global developmental delay (55% male; mean age = 36.8 months, 17–63 mo.). Visual microscopic examination and quantitative analyses showed extremely high epidermal nerve fiber density values for some children. Children with reported self-injury (5/11) had significantly (p < 0.02) greater density values (138.8, sd = 45.5) than children without self-injury (80.5, sd = 17.5). Results from this novel immunohistological analysis of skin in very young children with neurodevelopmental delays suggests it may be a useful tool to study peripheral innervation as a possible sensory risk factor for self-injury. PMID:25918119

Peripheral Innervation in Children With Global Developmental Delay: Biomarker for Risk for Self-Injurious Behavior?

PubMed

Symons, Frank J; Tervo, Raymond C; Barney, Chantel C; Damerow, John; Selim, Mona; McAdams, Brian; Foster, Shawn; Wendelschafer Crabb, Gwen; Kennedy, William

2015-11-01

The relation between somatosensory mechanisms and self-injury among children with neurologic impairments associated with developmental delay is not well understood. We evaluated the feasibility of procuring skin biopsies to examine epidermal nerve fiber density and reported self-injury. Following informed parental consent, epidermal skin biopsies were obtained from a distal leg site with no pre-existing skin damage from 11 children with global developmental delay (55% male; mean age = 36.8 months, 17-63 months). Visual microscopic examination and quantitative analyses showed extremely high epidermal nerve fiber density values for some children. Children with reported self-injury (5/11) had significantly (P < .02) greater density values (138.8, standard deviation = 45.5) than children without self-injury (80.5, standard deviation = 17.5). Results from this novel immunohistologic analysis of skin in very young children with neurodevelopmental delays suggest it may be a useful tool to study peripheral innervation as a possible sensory risk factor for self-injury. © The Author(s) 2015.

Early Effects of Responsivity Education/Prelinguistic Milieu Teaching for Children with Developmental Delays and Their Parents

ERIC Educational Resources Information Center

Fey, Marc E.; Warren, Steven F.; Brady, Nancy; Finestack, Lizbeth H.; Bredin-Oja, Shelley L.; Fairchild, Martha; Sokol, Shari; Yoder, Paul J.

2006-01-01

Purpose: To evaluate the efficacy of a 6-month course of responsivity education/prelinguistic milieu teaching (RE/PMT) for children with developmental delay and RE/PMT's effects on parenting stress in a randomized clinical trial. Method: Fifty-one children, age 24-33 months, with no more than 10 expressive words or signs, were randomly assigned to…