-
1.
Co-occurrence and Severity of Neurodevelopmental Burden (Cognitive Impairment, Cerebral Palsy, Autism Spectrum Disorder, and Epilepsy) at Age Ten Years in Children Born Extremely Preterm.
Hirschberger, RG, Kuban, KCK, O'Shea, TM, Joseph, RM, Heeren, T, Douglass, LM, Stafstrom, CE, Jara, H, Frazier, JA, Hirtz, D, et al
Pediatric neurology. 2018;:45-52
-
-
Free full text
-
Abstract
BACKGROUND This study aims to determine the prevalence of neurodevelopmental impairments at age ten years among children born extremely preterm (less than 28 weeks gestational age) and to offer a framework for categorizing neurological limitations. METHODS A multicenter, prospective cohort follow-up study recruited 889 ten-year-old children born from 2002 to 2004. We assessed prevalence of cognitive impairment, measured by intelligent quotient and tests of executive function, cerebral palsy (CP), autism spectrum disorder (ASD), and epilepsy singly and in combination. The three levels of impairment severity were: category I-no major neurodevelopmental impairment; category II-normal cognitive ability with CP, ASD, and/or epilepsy; and category III-children with cognitive impairment. RESULTS A total 214 of 873 children (25%) had cognitive impairment, 93 of 849 children (11%) had CP, 61 of 857 children (7%) had ASD, and 66 of 888 children (7%) had epilepsy. Further, 19% of all children had one diagnosis, 10% had two diagnoses, and 3% had three diagnoses. Decreasing gestational age was associated with increasing number of impairments (P < 0.001). Half the children with cognitive impairment and one third of children with CP, ASD, or epilepsy had a single impairment. Six hundred one (68% [95% CI, 64.5%-70.7%]) children were in category I, 74 (8% [95% CI, 6.6%-10.3%]) were in category II, and 214 (24% [95% CI 21.7%-27.4%]) were in category III. CONCLUSIONS Three quarters of children had normal intellect at age ten years; nearly 70% were free of neurodevelopmental impairment. Forty percent of children with impairments had multiple diagnoses.
-
2.
The genetics and molecular biology of fever-associated seizures or epilepsy.
Deng, H, Zheng, W, Song, Z
Expert reviews in molecular medicine. 2018;:e3
Abstract
Fever-associated seizures or epilepsy (FASE) is primarily characterised by the occurrence of a seizure or epilepsy usually accompanied by a fever. It is common in infants and children, and generally includes febrile seizures (FS), febrile seizures plus (FS+), Dravet syndrome (DS) and genetic epilepsy with febrile seizures plus (GEFSP). The aetiology of FASE is unclear. Genetic factors may play crucial roles in FASE. Mutations in certain genes may cause a wide spectrum of phenotypical overlap ranging from isolated FS, FS+ and GEFSP to DS. Synapse-associated proteins, postsynaptic GABAA receptor, and sodium channels play important roles in synaptic transmission. Mutations in these genes may involve in the pathogenesis of FASE. Elevated temperature promotes synaptic vesicle (SV) recycling and enlarges SV size, which may enhance synaptic transmission and contribute to FASE occurring. This review provides an overview of the loci, genes, underlying pathogenesis and the fever-inducing effect of FASE. It may provide a more comprehensive understanding of pathogenesis and contribute to the clinical diagnosis of FASE.
-
3.
[Specific aspects of the management of women with epilepsy].
Dupont, S
Presse medicale (Paris, France : 1983). 2018;(3):251-260
Abstract
Catamenial epilepsy, defined as the exacerbation of the frequency of seizures in a given phase of the menstrual cycle, affects 35% of women. In women with catamenial epilepsy with perimenstrual seizures, progesterone therapy may be effective. In case of enzyme inducer AEDs, hormonal contraception is deprecated (estroprogestative or progestative pill, progestative implant, patches or hormonal rings). Because of its high malformative teratogenic potential, its possible depressive cognitive effects and the autistic risk, sodium valproate is not indicated during pregnancy. To date, the most recommended AEDs for pregnancy are lamotrigine and levetiracetam. Plasma drug monitoring is recommended during pregnancy. The decision to breastfeed remains individual depending mainly on the term of delivery and the type of antiepileptic treatment.
-
4.
Methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to epilepsy.
Rai, V, Kumar, P
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2018;(12):2033-2041
Abstract
BACKGROUND Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism was reported as risk factor for multiple diseases due to its role in conversion of homocysteine to methionine. The aim of the present meta-analysis was to find out the validity of association of C677T polymorphism with epilepsy susceptibility. METHODS Pubmed, Science Direct, Springer Link and Google Scholar, databases were searched for relevant studies up to January, 31, 2018. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were performed using five genetic models. All statistical analysis was done by MetaAnalyst and Mix programs. RESULTS Except recessive model, significant association was found between MTHFR C677T polymorphism and epilepsy risk in other four genetic models (T vs C: OR = 1.29, 95% CI = 1.08-1.52, p = 0.004; TT vs CC: OR = 1.48, 95% CI = 1.19-1.82, p = 0.0003; TT + CT vs CC: OR = 1.20, 95% CI = 1.05-1.38, p = 0.008; TT vs CT + CC: OR = 1.35, 95% CI = 1.11-1.62, p = 0.002). Similarly, in the subgroup analysis based on ethnicity, significant association was found in Asian (T vs C: OR = 1.85; 95% CI = 1.15-2.99; p = 0.03) and Caucasian populations (TT vs CC: OR = 1.38; 95% CI = 1.10-1.1.73; p = 0.005). No evidence of heterogeneity and publication bias was detected in present meta-analysis. CONCLUSION In conclusion, results of present meta-analysis suggested that 677T allele of MTHFR is significantly increases the epilepsy susceptibility.
-
5.
Neuron dynamics variability and anomalous phase synchronization of neural networks.
Boaretto, BRR, Budzinski, RC, Prado, TL, Kurths, J, Lopes, SR
Chaos (Woodbury, N.Y.). 2018;(10):106304
Abstract
Anomalous phase synchronization describes a synchronization phenomenon occurring even for the weakly coupled network and characterized by a non-monotonous dependence of the synchronization strength on the coupling strength. Its existence may support a theoretical framework to some neurological diseases, such as Parkinson's and some episodes of seizure behavior generated by epilepsy. Despite the success of controlling or suppressing the anomalous phase synchronization in neural networks applying external perturbations or inducing ambient changes, the origin of the anomalous phase synchronization as well as the mechanisms behind the suppression is not completely known. Here, we consider networks composed of N=2000 coupled neurons in a small-world topology for two well known neuron models, namely, the Hodgkin-Huxley-like and the Hindmarsh-Rose models, both displaying the anomalous phase synchronization regime. We show that the anomalous phase synchronization may be related to the individual behavior of the coupled neurons; particularly, we identify a strong correlation between the behavior of the inter-bursting-intervals of the neurons, what we call neuron variability, to the ability of the network to depict anomalous phase synchronization. We corroborate the ideas showing that external perturbations or ambient parameter changes that eliminate anomalous phase synchronization and at the same time promote small changes in the individual dynamics of the neurons, such that an increasing individual variability of neurons implies a decrease of anomalous phase synchronization. Finally, we demonstrate that this effect can be quantified using a well known recurrence quantifier, the "determinism." Moreover, the results obtained by the determinism are based on only the mean field potential of the network, turning these measures more suitable to be used in experimental situations.
-
6.
Maternal Carbamazepine Therapy and Unusual Adverse Effects in a Breastfed Infant.
Antonucci, R, Cuzzolin, L, Manconi, A, Cherchi, C, Oggiano, AM, Locci, C
Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine. 2018;(2):155-157
Abstract
BACKGROUND Usually, no adverse effects are observed in breastfed infants whose mothers are treated with the anti-epileptic carbamazepine. In this article, we described unusual short-term adverse effects observed in a young infant after exposure to carbamazepine during pregnancy and lactation. CASE REPORT A 40-day-old female infant, born at term, was admitted to the Pediatric Clinic at University of Sassari, Italy, for recurrent regurgitations and vomiting. She was breastfed since birth and her mother was under chronic carbamazepine therapy. Gastroesophageal reflux was initially suspected; therefore, thickening of feeds and postural therapy were applied without any benefit. Subsequently, high levels of carbamazepine were detected in infant serum and in maternal breast milk. After an unsuccessful attempt to combine breastfeeding with formula feeding, the switch to exclusive formula feeding was made, with subsequent rapid resolution of symptoms and body weight increase. DISCUSSION AND CONCLUSIONS The use of carbamazepine is considered compatible with breastfeeding, even if the potential risk of adverse reactions in breastfed infants exists. In this case, the discontinuation of breastfeeding resulted in the complete resolution of symptoms, suggesting a correlation between the observed manifestations in the infant and her exposure to maternal therapy.
-
7.
A novel SLC1A4 homozygous mutation causing congenital microcephaly, epileptic encephalopathy and spastic tetraparesis: a video-EEG and tractography - case study.
Pironti, E, Salpietro, V, Cucinotta, F, Granata, F, Mormina, E, Efthymiou, S, Scuderi, C, Gagliano, A, Houlden, H, Di Rosa, G
Journal of neurogenetics. 2018;(4):316-321
Abstract
Biallelic mutations in the SLC1A4 gene have been identified as a very rare cause of neurodevelopmental disorders. l-serine transport deficiency has been regarded as the causal molecular mechanism underlying the neurological phenotype of SLC1A4 mutation patients. To date this genetic condition has been reported almost exclusively in a limited number of Ashkenazi-Jewish individuals and as a result the SLC1A4 gene is not routinely included in the majority of the genetic diagnostic panels for neurological diseases. We hereby report a 7-year-old boy from a Southern Italian family, presenting with epileptic encephalopathy, congenital microcephaly, global developmental delay, severe hypotonia, spasticity predominant at the lower limbs, and thin corpus callosum. Whole exome sequencing identified a novel segregating SLC1A4 gene homozygous mutation (c.1141G > A: p.Gly381Arg) as the likely cause of the disease in our family. In order to deeply characterize the electro-clinical and neurological phenotype in our index patient, long-term systematic video-electroencephalograms (EEG) as well as repeated brain imaging studies (which included tractographic reconstructions) were performed on a regular basis during a 7 years follow-up time. In conclusion, we suggest to carefully considering SLC1A4 biallelic mutations in individuals presenting an early onset severe neurodevelopmental disorder with variable spasticity and seizures, regardless the patients' ethnic background.
-
8.
SCN1A rs3812718 polymorphism is associated with epilepsy: An updated meta-analysis.
Zhi, H, Wu, C, Yang, Z
Epilepsy research. 2018;:81-87
Abstract
To clarify the association between SCN1A rs3812718 polymorphism and epilepsy, we performed an updated meta-analysis. PubMed, Science Direct, Embase, Springer, Google Scholar, and Cochrane databases were searched before January 20, 2018. Odds ratios and 95% confidence intervals were used to assess the strength of associations. Finally, simply eight studies were included in this meta-analysis and all together recruited 7184 individuals, and they consisted of 3595 cases and 3589 controls. Based on the quality evaluation with the NOS, the overall quality of eight studies was scored from seven to eight which indicated good quality. A significant association between SCN1A rs3812718 polymorphism and the risk of epilepsy was detected in the homozygote comparison (OR = 1.64, 95% CI, 1.25-2.15, P = .001, P(BON) = 0.004), and dominant model (OR = 1.36, 95% CI, 1.08-1.72, P < .001, P(BON) < 0.001), but not in heterozygote comparison (OR = 1.22, 95% CI, 0.98-1.53, P = .003, P(BON) = 0.001), and recessive model (OR = 1.35, 95% CI, 1.22-1.49, P = .104, P(BON) = 0.104). In conclusion, our results suggest that SCN1A rs3812718 polymorphism is associated with the risk of epilepsy.
-
9.
Early Life Epilepsy and Episodic Apnea Revealing an ATP1A3 Mutation: Report of a Pediatric Case and Literature Review.
Younes, TB, Benrhouma, H, Klaa, H, Rouissi, A, Chaabouni, M, Kraoua, I, Youssef-Turki, IB
Neuropediatrics. 2018;(5):339-341
Abstract
ATP1A3 mutations have now been recognized in infants, children, and adults presenting with a diverse group of neurological phenotypes, including rapid-onset dystonia-parkinsonism, alternating hemiplegia of childhood, and most recently, cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss syndrome. The phenotypic spectrum of ATP1A3-related neurological disorders continues to expand. In this case study, we report on early life epilepsy with episodic apnea potentially secondary to ATP1A3 mutation in a Tunisian child.
-
10.
Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data.
Nevitt, SJ, Sudell, M, Weston, J, Tudur Smith, C, Marson, AG
The Cochrane database of systematic reviews. 2017;(12):CD011412
-
-
Free full text
-
Abstract
BACKGROUND Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for partial onset seizures and sodium valproate for generalised onset seizures; however a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices. OBJECTIVES To compare the time to withdrawal of allocated treatment, remission and first seizure of 10 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide) currently used as monotherapy in children and adults with partial onset seizures (simple partial, complex partial or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus). SEARCH METHODS We searched the following databases: Cochrane Epilepsy's Specialised Register, CENTRAL, MEDLINE and SCOPUS, and two clinical trials registers. We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field. The date of the most recent search was 27 July 2016. SELECTION CRITERIA We included randomised controlled trials of a monotherapy design in adults or children with partial onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types). DATA COLLECTION AND ANALYSIS This was an individual participant data (IPD) review and network meta-analysis. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary outcomes were 'time to achieve 12-month remission', 'time to achieve six-month remission', 'time to first seizure post-randomisation', and 'occurrence of adverse events'. We presented all time-to-event outcomes as Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs). We performed pairwise meta-analysis of head-to-head comparisons between drugs within trials to obtain 'direct' treatment effect estimates and we performed frequentist network meta-analysis to combine direct evidence with indirect evidence across the treatment network of 10 drugs. We investigated inconsistency between direct estimates and network meta-analysis via node splitting. Due to variability in methods and detail of reporting adverse events, we have not performed an analysis. We have provided a narrative summary of the most commonly reported adverse events. MAIN RESULTS IPD was provided for at least one outcome of this review for 12,391 out of a total of 17,961 eligible participants (69% of total data) from 36 out of the 77 eligible trials (47% of total trials). We could not include IPD from the remaining 41 trials in analysis for a variety of reasons, such as being unable to contact an author or sponsor to request data, data being lost or no longer available, cost and resources required to prepare data being prohibitive, or local authority or country-specific restrictions.We were able to calculate direct treatment effect estimates for between half and two thirds of comparisons across the outcomes of the review, however for many of the comparisons, data were contributed by only a single trial or by a small number of participants, so confidence intervals of estimates were wide.Network meta-analysis showed that for the primary outcome 'Time to withdrawal of allocated treatment,' for individuals with partial seizures; levetiracetam performed (statistically) significantly better than current first-line treatment carbamazepine and other current first-line treatment lamotrigine performed better than all other treatments (aside from levetiracetam); carbamazepine performed significantly better than gabapentin and phenobarbitone (high-quality evidence). For individuals with generalised onset seizures, first-line treatment sodium valproate performed significantly better than carbamazepine, topiramate and phenobarbitone (moderate- to high-quality evidence). Furthermore, for both partial and generalised onset seizures, the earliest licenced treatment, phenobarbitone seems to perform worse than all other treatments (moderate- to high-quality evidence).Network meta-analysis also showed that for secondary outcomes 'Time to 12-month remission of seizures' and 'Time to six-month remission of seizures,' few notable differences were shown for either partial or generalised seizure types (moderate- to high-quality evidence). For secondary outcome 'Time to first seizure,' for individuals with partial seizures; phenobarbitone performed significantly better than both current first-line treatments carbamazepine and lamotrigine; carbamazepine performed significantly better than sodium valproate, gabapentin and lamotrigine. Phenytoin also performed significantly better than lamotrigine (high-quality evidence). In general, the earliest licenced treatments (phenytoin and phenobarbitone) performed better than the other treatments for both seizure types (moderate- to high-quality evidence).Generally, direct evidence and network meta-analysis estimates (direct plus indirect evidence) were numerically similar and consistent with confidence intervals of effect sizes overlapping.The most commonly reported adverse events across all drugs were drowsiness/fatigue, headache or migraine, gastrointestinal disturbances, dizziness/faintness and rash or skin disorders. AUTHORS' CONCLUSIONS Overall, the high-quality evidence provided by this review supports current guidance (e.g. NICE) that carbamazepine and lamotrigine are suitable first-line treatments for individuals with partial onset seizures and also demonstrates that levetiracetam may be a suitable alternative. High-quality evidence from this review also supports the use of sodium valproate as the first-line treatment for individuals with generalised tonic-clonic seizures (with or without other generalised seizure types) and also demonstrates that lamotrigine and levetiracetam would be suitable alternatives to either of these first-line treatments, particularly for those of childbearing potential, for whom sodium valproate may not be an appropriate treatment option due to teratogenicity.