Pediatrics Febrile Seizures Publications (1008)


Pediatrics Febrile Seizures Publications

Epilepsia 2017 Jan 13. Epub 2017 Jan 13.
Department of Medicine, Epilepsy Research Centre, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
J. Biol. Regul. Homeost. Agents
J Biol Regul Homeost Agents 2016 Oct-Dec;30(4):1217-1221
General Paediatrics O.U., Policlinico-Vittorio Emanuele University Hospital, University of Catania, Italy.

Congenital Muscular Dystrophies (CMDs) can be considered as a heterogeneous group of diseases characterized by marked weakness, generalized hypotonia and joint contractures. They are divided into pure and classical forms, without ocular and cerebral involvement, and complex forms, which are associated with cerebral abnormalities. Seizures have rarely been described in the pure forms while they seem to occur more frequently in complex forms. Read More

The aim of our study was to evaluate the incidence of seizure in CMD. Herein, the authors describe 16 cases of congenital muscular dystrophy (CMD) associated with different kinds of epileptic events, in order to study the pathogenic connection between the two clinical manifestations. In all described patients we reviewed the clinical, neurophysiologic, and neuroimaging data to determine any associations with epilepsy. The patients were divided into two groups: 14 cases with merosin positive CMD in one group and 2 patients with Walker Warburg syndrome (WWS) in the second group. In our study we found that in the first group, one benign myoclonic epilepsy (BME), one benign febrile convulsions had occurred. Also in one patient, the EEG revealed a moderately high voltage slow background with diffuse sharp waves reaching 300mV in amplitude with no clinical signs. In the merosin positive CMD patients, the presence of two different epileptic diseases, benign myoclonic epilepsy (BME) in one and febrile convulsion with tonic clinic seizures, may represent a new expression of merosine-positive congenital muscular disease (PCMD) in which the deficiency of an undiscovered muscular protein with a cerebral isoform may be the cause of epileptic events in this group of patients.

Ann Clin Transl Neurol
Ann Clin Transl Neurol 2017 Jan 20;4(1):26-35. Epub 2016 Dec 20.
Qatar Biomedical Research InstituteMedical Genetics CenterHamad Bin Khalifa UniversityDohaQatar; PediatricsUniversity of IowaIowa CityIowa; PediatricsUniversity of JordanAmmanJordan.

Two consanguineous families, one of Sudanese ethnicity presenting progressive neuromuscular disease, severe cognitive impairment, muscle weakness, upper motor neuron lesion, anhydrosis, facial dysmorphism, and recurrent seizures and the other of Egyptian ethnicity presenting with neonatal hypotonia, bradycardia, and recurrent seizures, were evaluated for the causative gene mutation.
Homozygosity mapping and whole exome sequencing (WES) identified damaging homozygous variants in SCN10A, namely c.4514C>T; p. Read More

Thr1505Met in the first family and c.4735C>T; p.Arg1579* in the second family. A third family, of Western European descent, included a child with febrile infection-related epilepsy syndrome (FIRES) who also had compound heterozygous missense mutations in SCN10A, namely, c.3482T>C; p.Met1161Thr and c.4709C>A; p.Thr1570Lys. A search for SCN10A variants in three consortia datasets (EuroEPINOMICS, Epi4K/EPGP, Autism/dbGaP) identified an additional five individuals with compound heterozygous variants. A Hispanic male with infantile spasms [c.2842G>C; p.Val948Leu and c.1453C>T; p.Arg485Cys], and a Caucasian female with Lennox-Gastaut syndrome [c.1529C>T; p.Pro510Leu and c.4984G>A; p.Gly1662Ser] in the epilepsy databases and three in the autism databases with [c.4009T>A; p.Ser1337Thr and c.1141A>G; p.Ile381Val], [c.2972C>T; p.Pro991Leu and c.2470C>T; p.His824Tyr], and [c.4009T>A; p.Ser1337Thr and c.2052G>A; p.Met684Ile].
SCN10A is a member of the voltage-gated sodium channel (VGSC) gene family. Sodium channels are responsible for the instigation and proliferation of action potentials in central and peripheral nervous systems. Heterozygous mutations in VGSC genes cause a wide range of epileptic and peripheral nervous system disorders. This report presents autosomal recessive mutations in SCN10A that may be linked to epilepsy-related phenotypes, Lennox-Gastaut syndrome, infantile spasms, and Autism Spectrum Disorder.

Epilepsy Behav Case Rep
Epilepsy Behav Case Rep 2017 9;7:16-19. Epub 2016 Nov 9.
Department of Neurosurgery, Graduate School of Medical and Dental Science, Kagoshima University, Kagoshima, Japan.

Genetic epilepsy with febrile seizures plus (GEFS(+)) is characterized by childhood-onset epilepsy syndrome. It involves febrile seizures and a variety of afebrile epileptic seizure types within the same pedigree with autosomal-dominant inheritance. Approximately 10% of individuals with GEFS(+) harbor SCN1A, a gene mutation in one of the voltage-gated sodium channel subunits. Read More

Considerably less common are focal epilepsies including complex partial seizures. We report vagus nerve stimulation (VNS) in a 6-year-old girl with GEFS(+) who exhibited refractory generalized tonic-clonic seizures and complex partial seizures.

Neurology 2017 Jan 4. Epub 2017 Jan 4.
From the Danish Epilepsy Centre (R.S.M., K.M.J., M.N.), Dianalund; Institute for Regional Health Services (R.S.M., K.M.J., M.N.), University of Southern Denmark, Odense; Department of Neurology and Epileptology (T.V.W., S.V., H.L., S.M.), Hertie Institute for Clinical Brain Research, and Department of Neurosurgery (T.V.W.), University of Tübingen; Department of Neuropediatrics (I.H., M.P., S.v.S., H.M.), University Medical Center Schleswig-Holstein, Kiel, Germany; Division of Neurology (I.H., S.H., H.D.), The Children's Hospital of Philadelphia, PA; Neuroscience Department (C.M., R.G.), Children's Hospital Anna Meyer-University of Florence, Italy; Department of Genetics (E.H.B., M.S., K.L.v.G.), University Medical Center Utrecht, the Netherlands; Department of Neurology and Neurorehabilitation (U.V., I.T., T.T.), Children's Clinic of Tartu University Hospital, Estonia; Department of Pediatric Neurology and Epilepsy Center (I.B.), LMU Munich, Germany; Department of Pediatrics (I.T., T.T.), University of Tartu; Tallinn Children's Hospital (I.T.), Tallinn, Estonia; Clinic for Neuropediatrics and Neurorehabilitation (G.K., C.B., H.H.), Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Germany; Paracelsus Medical Private University (G.K.), Salzburg, Austria; Neuropeadiatric Department (L.L.F.), Hospices Civils de Lyon; Department of Genetics (G.L., N.C.), Lyon University Hospitals; Claude Bernard Lyon I University (G.L., N.C.); Lyon Neuroscience Research Centre (G.L., N.C.), CNRS UMR5292, INSERM U1028; Epilepsy, Sleep and Pediatric Neurophysiology Department (J.d.B.), Lyon University Hospitals, France; Clinic for Pediatric Neurology (S.B.), Pediatric Department, University Hospital, Herlev, Denmark; Kleinwachau (N.H.), Sächsisches Epilepsiezentrum Radeberg, Dresden; Department of Neuropediatrics/Epilepsy Center (J.J.), University Medical Center Freiburg; Department of General Paediatrics (S.S.), Division of Child Neurology and Inherited Metabolic Diseases, Centre for Paediatrics and Adolescent Medicine, University Hospital Heidelberg; Department of Women and Child Health (S.S.), Hospital for Children and Adolescents, University of Leipzig Hospitals and Clinics, Germany; Department of Pediatrics (C.T.M., H.C.M.), Division of Genetic Medicine, University of Washington, Seattle; Amplexa Genetics (L.H.G.L., H.A.D.), Odense, Denmark; Northern German Epilepsy Center for Children and Adolescents (S.v.S.), Schwentinental-Raisdorf, Germany; Wilhelm Johannsen Centre for Functional Genome Research (Y.M., N.T.), Department of Cellular and Molecular Medicine, University of Copenhagen; Danish Epilepsy Center (G.R.), Filadelfia/University of Copenhagen, Denmark; Department of Diagnostics (J.R.L.), Institute of Human Genetics, University of Leipzig; and Svt. Luka's Institute of Child Neurology and Epilepsy (K.M.), Moscow, Russia. Dr Maljevic is currently at the Florey Institute of Neuroscience and Mental Health, Melbourne, Australia.

To examine the role of mutations in GABRB3 encoding the β3 subunit of the GABAA receptor in individual patients with epilepsy with regard to causality, the spectrum of genetic variants, their pathophysiology, and associated phenotypes.
We performed massive parallel sequencing of GABRB3 in 416 patients with a range of epileptic encephalopathies and childhood-onset epilepsies and recruited additional patients with epilepsy with GABRB3 mutations from other research and diagnostic programs.
We identified 22 patients with heterozygous mutations in GABRB3, including 3 probands from multiplex families. Read More

The phenotypic spectrum of the mutation carriers ranged from simple febrile seizures, genetic epilepsies with febrile seizures plus, and epilepsy with myoclonic-atonic seizures to West syndrome and other types of severe, early-onset epileptic encephalopathies. Electrophysiologic analysis of 7 mutations in Xenopus laevis oocytes, using coexpression of wild-type or mutant β3, together with α5 and γ2s subunits and an automated 2-microelectrode voltage-clamp system, revealed reduced GABA-induced current amplitudes or GABA sensitivity for 5 of 7 mutations.
Our results indicate that GABRB3 mutations are associated with a broad phenotypic spectrum of epilepsies and that reduced receptor function causing GABAergic disinhibition represents the relevant disease mechanism.

Korean J Pediatr
Korean J Pediatr 2016 Nov 30;59(Suppl 1):S133-S138. Epub 2016 Nov 30.
Department of Pediatrics, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.

Anti-N-methyl D-aspartate receptor (anti-NMDAR) encephalitis, recently recognized as a form of paraneoplastic encephalitis, is characterized by a prodromal phase of unspecific illness with fever that resembles a viral disease. The prodromal phase is followed by seizures, disturbed consciousness, psychiatric features, prominent abnormal movements, and autonomic imbalance. Here, we report a case of anti-NMDAR encephalitis with initial symptoms of epilepsia partialis continua in the absence of tumor. Read More

Briefly, a 3-year-old girl was admitted to the hospital due to right-sided, complex partial seizures without preceding febrile illness. The seizures evolved into epilepsia partialis continua and were accompanied by epileptiform discharges from the left frontal area. Three weeks after admission, the patient's seizures were reduced with antiepileptic drugs; however, she developed sleep disturbances, cognitive decline, noticeable oro-lingual-facial dyskinesia, and choreoathetoid movements. Anti-NMDAR encephalitis was confirmed by positive detection of NMDAR antibodies in the patient's serum and cerebrospinal fluid, and her condition slowly improved with immunoglobulin, methylprednisolone, and rituximab. At present, the patient is no longer taking multiple antiepileptic or antihypertensive drugs. Moreover, the patient showed gradual improvement of motor and cognitive function. This case serves as an example that a diagnosis of anti-NMDAR encephalitis should be considered when children with uncontrolled seizures develop dyskinesias without evidence of malignant tumor. In these cases, aggressive immunotherapies are needed to improve the outcome of anti-NMDAR encephalitis.

Korean J Pediatr
Korean J Pediatr 2016 Nov 30;59(Suppl 1):S14-S18. Epub 2016 Nov 30.
Department of Pediatrics, Dankook University Hospital, Cheonan, Korea.

Pediatric epilepsy can be caused by various conditions, including specific syndromes. 1p36 deletion syndrome is reported in 1 in 5,000-10,000 newborns, and its characteristic clinical features include developmental delay, mental retardation, hypotonia, congenital heart defects, seizure, and facial dysmorphism. However, detection of the terminal deletion in chromosome 1p by conventional G-banded karyotyping is difficult. Read More

Here we present a case of epilepsy with profound developmental delay and characteristic phenotypes. A 7-year- and 6-month-old boy experienced afebrile generalized seizure at the age of 5 years and 3 months. He had recurrent febrile seizures since 12 months of age and showed severe global developmental delay, remarkable hypotonia, short stature, and dysmorphic features such as microcephaly; small, low-set ears; dark, straight eyebrows; deep-set eyes; flat nasal bridge; midface hypoplasia; and a small, pointed chin. Previous diagnostic work-up, including conventional chromosomal analysis, revealed no definite causes. However, array-comparative genomic hybridization analysis revealed 1p36 deletion syndrome with a 9.15-Mb copy loss of the 1p36.33-1p36.22 region, and fluorescence in situ hybridization analysis (FISH) confirmed this diagnosis. This case highlights the need to consider detailed chromosomal study for patients with delayed development and epilepsy. Furthermore, 1p36 deletion syndrome should be considered for patients presenting seizure and moderate-to-severe developmental delay, particularly if the patient exhibits dysmorphic features, short stature, and hypotonia.

Seizure 2016 Dec 1;45:70-73. Epub 2016 Dec 1.
Department of Paediatrics, University Hospital Rigshospitalet, Copenhagen, Denmark; Danish Epilepsy Centre, Dianalund, Denmark.

Epilepsy surgery is performed based on the assumption that medical refractory epilepsy will continue. Rarely seizure freedom occurs before surgery is performed, while the patient is being evaluated as an epilepsy surgery candidate. The aim of this study was to describe the number of children withdrawn from an epilepsy surgery programme due to unexpected seizure improvement. Read More

We retrospectively studied 173 children under 18 years with medical refractory epilepsy referred for epilepsy surgery between 1996 and 2010. Medical records were reviewed in 2012 and 2015.
At the first evaluation point in 2012, 13 patients were withdrawn from the epilepsy surgery programme due to unexpected marked improvement. In 2015, 6 of them were still seizure free. They had unexpected seizure freedom due to change in AED treatment (n=3) or after a febrile episode (n=3). The mean number of years they had had seizures was 3.4 years (range 0.6-6.2 years) and the number of seizures at inclusion was 209 per month (range 6-750 per month). The duration of follow-up was 6.6 years after inclusion into the epilepsy surgery programme (range 4.0-13.0 years). The aetiology of the epilepsy for these patients was heterotopia (n=1), focal cortical dysplasia (n=3), infarction (n=1) and unknown, with normal MRI (n=1). They all had an IQ in the normal range. Two of the remaining 7 children were operated later.
Unexpected seizure control may occur during epilepsy surgery evaluation.

Febrile seizures (FS) involve 2-5% of the paediatric population, among which Complex FS (CFS) account for one third of accesses for FS in Emergency Departments (EDs). The aim of our study was to define the epidemiology, the clinical, diagnostic and therapeutic approach to FS and CFSs in the Italian EDs.
A multicenter prospective observational study was performed between April 2014 and March 2015. Read More

Patients between 1 and 60 months of age, randomly accessing to ED for ongoing FS or reported FS at home were included. Demographic features and diagnostic-therapeutic follow-up were recorded. FS were categorized in simple (<10min), prolonged (10-30min) and status epilepticus (>30min).
The study population consisted of 268 children. Most of the children experienced simple FS (71.65%). Among the 68 (25.37%) patients with complex FS, 11 were 6-12 month-old, accounting for 45.83% of all the infants with FS in the younger age group. No therapy has been administered at home in 76.12% patients; 23.51% of them received endorectal diazepam and only 1 patient received buccal midazolam. At arrival at ED, no therapy was necessary for 70.52% patients; 50.63% received endorectal diazepam and 17.72% an i.v. bolus of midazolam. Blood tests and acid-base balanced were performed respectively in 82.09% of cases. An electroencephalogram at ED was performed in 21.64% of patients. Neuroimagings were done in 3.73% of cases. A neurologic consultation was asked for 36 patients (13.43%).
this is the first study assessing epidemiologic characteristics of FS in the Italian pediatric population, evidencing a higher prevalence of CFSs in children younger than 12 months of age and opening a new research scenario on the blood brain barrier vulnerability. On a national level, our study showed the need for a diagnostic standardized work-up to improve the cost/benefit ratio on CFS management.

Neuropediatrics 2016 Dec 5. Epub 2016 Dec 5.
Neuropediatric Clinic and Clinic for Neurorehabilitation, Epilepsy Center for Children and Adolescents, Vogtareuth, Germany.