Acute encephalopathy with biphasic seizures and late reduced diffusion; posterior frontal hyperperfusion before late seizures revealed by arterial spin labeling: A case report.

BACKGROUND: Arterial spin labeling, a magnetic resonance imaging modality that can evaluate cerebral perfusion without using a contrast material or ionizing radiation, is becoming increasingly accessible. However, only a few reports have used this method to assess the perfusion abnormalities observed in acute encephalopathy with biphasic seizures and late reduced diffusion. PATIENT DESCRIPTION: A 10-month-old Japanese girl presented with febrile status epilepticus (early seizures). Her convulsions ceased after the administration of intravenous phenobarbital, although her impaired consciousness was protracted. Five days later, diffusion-weighted imaging revealed slightly high signal intensity lesions in the bilateral posterior frontal areas. Arterial spin labeling revealed bilateral frontal-dominant hypoperfusion and posterior frontal hyperperfusion. On day 6, she had three convulsions (late seizures) and was diagnosed with acute encephalopathy with biphasic seizures and late reduced diffusion. She received treatment accordingly and recovered eventually. DISCUSSION: Based on previous reports, hypoperfusion within 1-2 days of early seizures and hyperperfusion accompanied by bright tree appearance on diffusion-weighted imaging within 1-2 days of late seizures are typical in acute encephalopathy with biphasic seizures and late reduced diffusion. In our patient, the first magnetic resonance imaging scan was performed one day prior to the onset of late seizures. We observed posterior frontal hyperperfusion accompanied by high signals on diffusion-weighted imaging, which leads us to speculate that this could be a predictive marker of late seizures.

Phenotypic spectrum of patients with GABRB2 variants: from mild febrile seizures to severe epileptic encephalopathy.

AIM: To characterize the different phenotypes of GABRB2-related epilepsy and to establish a genotype-phenotype correlation. METHOD: We used next-generation sequencing to identify GABRB2 variants in 15 patients. RESULTS: Eleven GABRB2 variants were novel and 12 were de novo. The age at the onset of seizures ranged from 1 day to 26 months. Nine patients had multiple seizure types, including focal seizures, generalized tonic-clonic seizures, myoclonic seizures, epileptic spasms, and atonic seizures. Seizures were fever-sensitive in 13 out of the 15 patients. Eleven patients displayed developmental delay, while 11 had abnormal video electroencephalography. Abnormalities in the brain images included dysplasia of the frontal and temporal cortex, dysplasia of the corpus callosum, and delayed myelination in four patients. One patient was diagnosed with febrile seizures, three with febrile seizures plus, three with Dravet syndrome, three with West syndrome, one with Ohtahara syndrome, three with developmental delays and epilepsy, and one with non-specific early-onset epileptic encephalopathy. INTERPRETATION: The most common phenotypes of patients with GABRB2 variants include early onset of seizure and fever sensitivity. Febrile seizures and febrile seizures plus are new phenotypes of GABRB2 variants. The phenotypic spectrum of GABRB2 variants ranges from mild febrile seizures to severe epileptic encephalopathy.

Protective effects of maternal administration of curcumin and hesperidin in the rat offspring following repeated febrile seizure: Role of inflammation and TLR4.

Neuroinflammation has a key role in seizure generation and perpetuation in the neonatal period, and toll-like receptor 4 (TLR4) pathway has a prominent role in neuroinflammatory diseases. Administration of antioxidants and targeting TLR4 in the embryonic period may protect rat offspring against the next incidence of febrile seizure and its harmful effects. Curcumin and hesperidin are natural compounds with anti-inflammatory and antioxidant properties and have an inhibitory action on TLR4 receptors. We evaluated the effect of maternal administration of curcumin and hesperidin on infantile febrile seizure and subsequent memory dysfunction in adulthood. Hyperthermia febrile seizure was induced on postnatal days 9-11 on male rat pups with 24 h intervals, in a Plexiglas box that was heated to ~45 °C by a heat lamp. We used enzyme-linked immunosorbent assay, Western blotting, malondialdehyde (MDA), and glutathione (GSH) assessment for evaluation of inflammatory cytokine levels, TLR4 protein expression, and oxidative responses in the hippocampal tissues. For assessing working memory and long-term potentiation, the double Y-maze test and Schaffer collateral-CA1 in vivo electrophysiological recording were performed, respectively Our results showed that curcumin and hesperidin decreased TNF-α, IL-10, and TLR4 protein expression and reversed memory dysfunction. However, they did not provoke a significant effect on GSH content or amplitude and slope of recorded fEPSPs in the hippocampus. In addition, curcumin, but not hesperidin, decreased interleukin-1ß (IL-1ß) and MDA levels. These findings imply that curcumin and hesperidin induced significant protective effects on febrile seizures, possibly via their anti-inflammatory and antioxidant properties and downregulation of TLR4.

A qPCR expression assay of IFI44L gene differentiates viral from bacterial infections in febrile children.

The diagnosis of bacterial infections in hospital settings is currently performed using bacterial culture from sterile site, but they are lengthy and limited. Transcriptomic biomarkers are becoming promising tools for diagnosis with potential applicability in clinical settings. We evaluated a RT-qPCR assay for a 2-transcript host expression signature (FAM89A and IFI44L genes) inferred from microarray data that allow to differentiate between viral and bacterial infection in febrile children. This assay was able to discriminate viral from bacterial infections (P-value = 1.04 × 10-4; AUC = 92.2%; sensitivity = 90.9%; specificity = 85.7%) and showed very high reproducibility regardless of the reference gene(s) used to normalize the data. Unexpectedly, the monogenic IFI44L expression signature yielded better results than those obtained from the 2-transcript test (P-value = 3.59 × 10-5; AUC = 94.1%; sensitivity = 90.9%; specificity = 92.8%). We validated this IFI44L signature in previously published microarray and whole-transcriptome data from patients affected by different types of viral and bacterial infections, confirming that this gene alone differentiates between both groups, thus saving time, effort, and costs. Herein, we demonstrate that host expression microarray data can be successfully translated into a fast, highly accurate and relatively inexpensive in vitro assay that could be implemented in the clinical routine.

Acetylcholine receptor agonist effect on seizure activity and GABAergic mechanisms involved in prolonged febrile seizure development in an animal model.

Febrile seizures are a paediatric condition which affects 2-5 % of children worldwide with prolonged febrile seizures (PFS) being found to cause long-term complications and predispose patients to other neurological conditions later in life. Febrile seizures occur due to an imbalance between the excitatory neurotransmitter glutamate and the inhibitory neurotransmitter GABA. α7-nicotinic acetylcholine receptors (α7-nAchRs) have been found to mediate GABA release as well as its neurotransmission. In this study, α7-nAchRs were activated by using PNU-282,987 (PNU), a selective α7-nAchR agonist, in order to evaluate their effect in seizure threshold as well as GABAergic parameters in a PFS rat model. PFS was induced on 14-day old Sprague-Dawley rat pups by administration of lipopolysaccharide (217 ug/kg, i.p) followed 2.5 h later by kainic acid (KA) (1.83 mg/kg, i.p). PNU was given prior to KA administration and Methyllycaconitine (MLA), an α7-nAchR antagonist, was given following KA injection. Seizure activity was recorded and monitored for one hour following seizure induction. Glutamate decarboxylase (GAD)1 and GAD 2 expression, as well as GABA concentration in the hippocampus, were assessed. Our results show that activating α7-nAchRs delays PFS progression and this delay was attenuated by the antagonist, MLA. Exposure to PFS reduced the expression of GAD1 and GABA concentration while PNU injection prevented this decrease. This suggests that specific nicotinic acetylcholine receptors may be used as therapeutic targets in the maintenance of adequate hippocampal GABA concentration for the prevention of PFS development.

Novel ANKRD11 gene mutation in an individual with a mild phenotype of KBG syndrome associated to a GEFS+ phenotypic spectrum: a case report.

BACKGROUND: KBG syndrome is a very rare autosomal dominant disorder, characterized by macrodontia, distinctive craniofacial findings, skeletal findings, post-natal short stature, and developmental delays, sometimes associated with seizures and EEG abnormalities. So far, there have been over 100 cases of KBG syndrome reported. CASE PRESENTATION: Here, we describe two sisters of a non-consanguineous family, both presenting generalized epilepsy with febrile seizures (GEFS+), and one with a more complex phenotype associated with mild intellectual disability, skeletal and dental anomalies. Whole exome sequencing (WES) analysis in all the family members revealed a heterozygous SCN9A mutation, p.(Lys655Arg), shared among the father and the two probands, and a novel de novo loss of function mutation in the ANKRD11 gene, p.(Tyr1715*), in the proband with the more complex phenotype. The reassessment of the phenotypic features confirmed that the patient fulfilled the proposed diagnostic criteria for KBG syndrome, although complicated by early-onset isolated febrile seizures. EEG abnormalities with or without seizures have been reported previously in some KBG cases. The shared variant, occurring in SCN9A, has been previously found in several individuals with GEFS+ and Dravet syndrome. CONCLUSIONS: This report describe a novel de novo variant in ANKRD11 causing a mild phenotype of KGB syndrome and further supports the association of monogenic pattern of SCN9A mutations with GEFS+. Our data expand the allelic spectrum of ANKRD11 mutations, providing the first Brazilian case of KBG syndrome. Furthermore, this study offers an example of how WES has been instrumental allowing us to better dissect the clinical phenotype under study, which is a multilocus variation aggregating in one proband, rather than a phenotypic expansion associated with a single genomic locus, underscoring the role of multiple rare variants at different loci in the etiology of clinical phenotypes making problematic the diagnostic path. The successful identification of the causal variant in a gene may not be sufficient, making it necessary to identify other variants that fully explain the clinical picture. The prevalence of blended phenotypes from multiple monogenic disorders is currently unknown and will require a systematic re-analysis of large WES datasets for proper diagnosis in daily practice.

Trend of subsequent epilepsy in children with recurrent febrile seizures: A retrospective matched cohort study.

PURPOSE: Trends of epilepsy in children were correlated with febrile seizure (FS) in a previous retrospective study. In the present study, the authors obtained relevant data from a nationwide cohort database to investigate trends in subsequent epilepsy in children with a history of recurrent FS. METHODS: A total of 10,210 children with FS comprised the cohort. The diagnosis date was used as the index date. A comparison cohort was randomly matched with each case based on age, sex, urbanization level, parents' occupation, and index date. Cox proportional hazard regression was performed to estimate the hazard ratio and confidence interval of FS-associated epilepsy. RESULTS: This retrospective cohort study included 7729 children with FS and a comparison cohort of 30,916 children. The incidence of epilepsy was 11.4-fold higher in the FS cohort than in the comparison cohort (5.67 vs. 0.49 per 1000 person-years, respectively). Compared with the comparison cohort, the epilepsy incidence rate ratio increased in children with admissions for FS, from 8.62 at 1 admission to 26.2 at ≥2 admissions (95% CI 6.80-10.9, and 19.78-34.8, respectively; p for trend < 0.0001). CONCLUSION: FS may increase the risk for subsequent epilepsy in children. Recurrent FS increased the cumulative incidence of epilepsy.

Electroencephalographic and biochemical long-lasting abnormalities in animal model of febrile seizure.

Febrile seizures (FS) are convulsions associated with high body temperature. It has a high incidence in children from the age of 6months to 5years and may have adverse consequences in adulthood. The experimental model of FS could be induced in animals via hyperthermia. The present study was designed to investigate persistent electroencephalographic (EEG), neurochemical and behavioral alterations in adult animals that had experienced complex FS at their immature age. EEG signals were obtained from the cortex of both FS and control normothermic groups of animals. A spectrophotometric assay was carried out to determine oxidative stress parameters (malondialdehyde, nitric oxide, reduced glutathione) and acetylcholinesterase activity in the cortex and hippocampus of FS and control animals. Behavioral assessment of seizure threshold and severity were investigated via a sub-convulsive dose of nicotine in adult animals. Alterations in the oxidant/antioxidant system and AChE activity were obtained in the cortex and hippocampus of FS animals in comparison to control animals. EEG spectral analysis displayed significant changes in all EEG frequency bands. A decrease in seizure latency and an increase in seizure severity were also observed. The present study provides evidence for long-lasting abnormalities in the cortex and hippocampus of adult animals subjected to complex FS at their developmental age, which may be correlated to the underlying mechanism of epileptogenesis and its related co-morbidities.

Reducing premature KCC2 expression rescues seizure susceptibility and spine morphology in atypical febrile seizures.

Atypical febrile seizures are considered a risk factor for epilepsy onset and cognitive impairments later in life. Patients with temporal lobe epilepsy and a history of atypical febrile seizures often carry a cortical malformation. This association has led to the hypothesis that the presence of a cortical dysplasia exacerbates febrile seizures in infancy, in turn increasing the risk for neurological sequelae. The mechanisms linking these events are currently poorly understood. Potassium-chloride cotransporter KCC2 affects several aspects of neuronal circuit development and function, by modulating GABAergic transmission and excitatory synapse formation. Recent data suggest that KCC2 downregulation contributes to seizure generation in the epileptic adult brain, but its role in the developing brain is still controversial. In a rodent model of atypical febrile seizures, combining a cortical dysplasia and hyperthermia-induced seizures (LHS rats), we found a premature and sustained increase in KCC2 protein levels, accompanied by a negative shift of the reversal potential of GABA. In parallel, we observed a significant reduction in dendritic spine size and mEPSC amplitude in CA1 pyramidal neurons, accompanied by spatial memory deficits. To investigate whether KCC2 premature overexpression plays a role in seizure susceptibility and synaptic alterations, we reduced KCC2 expression selectively in hippocampal pyramidal neurons by in utero electroporation of shRNA. Remarkably, KCC2 shRNA-electroporated LHS rats show reduced hyperthermia-induced seizure susceptibility, while dendritic spine size deficits were rescued. Our findings demonstrate that KCC2 overexpression in a compromised developing brain increases febrile seizure susceptibility and contribute to dendritic spine alterations.

Acute encephalitis with refractory, repetitive partial seizures: Pathological findings and a new therapeutic approach using tacrolimus.

Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is characterized by prolonged severe seizures and a high-grade fever. We experienced a boy with severe AERRPS with frequent partial seizures that exhibited right-side predominance. The patient required the continuous intravenous administration of many antiepileptic drugs and respirator management for several months. Methylprednisolone pulse therapy and intravenous immunoglobulin administration were only temporarily effective. The MRI and EEG showed the abnormality in the left occipital lobe. Although occipital lobectomy was performed, his seizures continued. His cerebrospinal fluid exhibited elevated protein and proinflammatory cytokine levels, and was positive for anti-glutamate receptor ε2 antibodies. Pathological examination showed infiltration of many neutrophilic leukocytes, T cells, and microglia in the area exhibiting severe spongiosis. We thought that the exaggerated microglia and T-cell responses were related to the pathogenesis of the patient's seizures, and we therefore initiated treatment with tacrolimus. As a result, many of the daily seizure clusters were ameliorated, and the patient was discharged. We attempted to discontinue the tacrolimus twice, but the patient's seizure clusters recurred each time. This is the first case report of the pathological findings of AERRPS and showing an effective therapeutic approach using tacrolimus. Tacrolimus may be an effective immunosuppressant, especially for patients with severe AERRPS.

Hyperthermia-induced seizures alter adenosine A1 and A2A receptors and 5'-nucleotidase activity in rat cerebral cortex.

Febrile seizure is one of the most common convulsive disorders in children. The neuromodulator adenosine exerts anticonvulsant actions through binding adenosine receptors. Here, the impact of hyperthermia-induced seizures on adenosine A1 and A2A receptors and 5'-nucleotidase activity has been studied at different periods in the cerebral cortical area by using radioligand binding, real-time PCR, and 5'-nucleotidase activity assays. Hyperthermic seizures were induced in 13-day-old rats using a warmed air stream from a hair dryer. Neonates exhibited rearing and falling over associated with hindlimb clonus seizures (stage 5 on Racine scale criteria) after hyperthermic induction. A significant increase in A1 receptor density was observed using [(3) H]DPCPX as radioligand, and mRNA coding A1 was observed 48 h after hyperthermia-induced seizures. In contrast, a significant decrease in A2A receptor density was detected, using [(3) H]ZM241385 as radioligand, 48 h after hyperthermia-evoked convulsions. These short-term changes in A1 and A2A receptors were also accompanied by a loss of 5'-nucleotidase activity. No significant variations either in A1 or A2A receptor density or 5'-nucleotidase were observed 5 and 20 days after hyperthermic seizures. Taken together, both regulation of A1 and A2A receptors and loss of 5'-nucleotidase in the cerebral cortex suggest the existence of a neuroprotective mechanism against seizures. Febrile seizure is one of the most common convulsive disorders in children. The consequences of hyperthermia-induced seizures (animal model of febrile seizures) on adenosine A1 and A2A receptors and 5'-nucleotidase activity have been studied at different periods in cerebral cortical area. A significant increase in A1 receptor density and mRNA coding A1 was observed 48 h after hyperthermia-induced seizures. In contrast, a significant decrease in A2A receptor density and 5'-nucleotidase activity was detected 48 h after convulsions evoked by hyperthermia. These changes suggest the possible existence of a neuroprotective mechanism against seizures.

Sudden infant death syndrome, sleep, and seizures.

WORKING HYPOTHESIS: benign febrile seizures seen in 7% of infants before 6 months play a role in the terminal pathway in a subset of sudden infant death syndrome victims. Supporting evidence: (1) lack of 5-hydroxitryptamine, one consistent finding in sudden infant death syndrome that Kinney et al coined a developmental serotonopathy, is consistent with risk for seizures. (2) Non-rapid eye movement sleep increasing during the age of highest risk for sudden infant death syndrome facilitates some seizures (seizure gate). (3) Sudden unexpected death in epilepsy is associated with severe hypoxemia and hypercapnia during postictal generalized electroencephalographic (EEG) suppression. In toddlers, sudden unexplained deaths are associated with hippocampal abnormalities and some seizures. (4) The sudden nature of both deaths warrants an exploration of similarities in the terminal pathway. Moreover, sudden infant death syndrome, febrile seizures, sudden unexplained death in childhood, and sudden unexpected death in epilepsy share some of the following risk factors: prone sleeping, infections, hyperthermia, preterm birth, male gender, maternal smoking, and mutations in genes that regulate sodium channels. State-of-the-art molecular studies can be exploited to test this hypothesis.

A postnatal peak in microglial development in the mouse hippocampus is correlated with heightened sensitivity to seizure triggers.

BACKGROUND: Explosive synaptogenesis and synaptic pruning occur in the hippocampus during the first two weeks of postnatal life, coincident with a heightened susceptibility to seizures in rodents. To determine the temporal correlation between microglial development and age-dependent susceptibility and response to seizures, we quantified developmental changes in basal microglia levels and seizure-induced microglial activation in the hippocampus of Cx3Cr1(GFP /+) transgenic mice. METHODS: Basal levels of microglia were quantified in the hippocampi of Cx3Cr1(GFP /+) mice at P0, P5, P10, P15, P20, P25, P30, P40, and P60. Seizure susceptibility and seizure-induced microglial activation were assessed in response to febrile seizures (lipopolysaccharide followed by hyperthermia) and kainic acid-induced status epilepticus. RESULTS: The density of microglia within the hippocampus increased rapidly after birth, reaching a peak during the second week of life - the age at which the animals became most vulnerable to seizure triggers. In addition, this peak of microglial development and seizure vulnerability during the second postnatal week represented the time of maximal seizure-induced microglia activation. CONCLUSIONS: Overreactive innate immunity mediated by activated microglia may exacerbate acute injury to neuronal synapses and contribute to the long-term epileptogenic effects of early-life seizures. Anti-inflammatory therapy targeting excessive production of inflammatory mediators by activated microglia, therefore, may be an effective age-specific therapeutic strategy to minimize neuronal dysfunction and prevent increases in susceptibility to subsequent seizures in developing animals.

Long-term modifications of epileptogenesis and hippocampal rhythms after prolonged hyperthermic seizures in the mouse.

Complex febrile seizures are often reported in the history of patients with mesio-temporal lobe epilepsy (MTLE) but their role in its physiopathology remains controversial. We postulated that prolonged hyperthermic seizures might, as a "single-hit", modify the hippocampal rhythms, facilitate epileptogenesis and influence subsequent epilepsy when a second-hit already exists or subsequently occurs. To test this hypothesis, we examined the effects of hyperthermic seizures (30min at 40-41°C) at postnatal day 10 on hippocampal activity in C57BL/6J mice in comparison to their littermates in sham conditions (22°C), with or without another insult. Using local field potential, we observed an asymmetry in the hippocampal susceptibility to seize in hyperthermic conditions. When these mice were adult, an asymmetrical increase of low frequency power was also recorded in the hippocampus when compared to sham animals. Using two different "two-hit" protocols, no increase in seizures or hippocampal discharge frequency or duration was observed, either in mice with a genetic CA3 dysplasia (Dcx knockout), or in mice injected with kainate into the dorsal hippocampus at P60. However, in the latter condition, which is reminiscent of MTLE, the hyperthermic seizures accelerated epileptogenesis and decreased the power in the high frequency gamma band, as well as decreasing the coherence between hippocampi and the involvement of the contralateral hippocampus during hippocampal paroxysmal discharges. Our data suggest that a single episode of prolonged hyperthermic seizures does not induce per se, but accelerates epileptogenesis and could lead to an asymmetrical dysfunction in the hippocampal rhythmicity in both physiological and pathological conditions.

[Simple febrile seizure, complex seizure, generalized epilepsy with febrile seizure plus, FIRES and new syndromes]. / Crisis febriles simples y complejas, epilepsia generalizada con crisis febriles plus, FIRES y nuevos síndromes.

Febrile seizures are the most common seizures in childhood. They have been observed in 2-5% of children before the age of 5, but in some populations this figure may increase to 15%. It is a common cause of pediatric hospital admissions and cause of anxiety for parents. Febrile seizures could be the first manifestation of epilepsy. About 13% of epileptic patients have a history of febrile seizure, and 30% have had recurrent febrile seizures. Their phenotypic characteristics allow, in the majority of cases, a classification of the seizure, an elaboration of a prognosis and to assume a specific therapeutic attitude. It is possible to describe a spectrum according to their severity, from the benign simple seizure to the more complex, febrile seizure plus, Dravet'syndrome, and FIRES. During the past decade, molecular genetic studies have contributed to the identification of genetic factors involved in febrile seizure and related disorders, making the necessity of a careful follow up of these patients in order to detect risk factors earlier. We have reviewed the medical literature to update current knowledge of febrile seizures, their prognosis and their relation to new epileptic syndromes.

[Cytokines and the nervous system: the relationship between seizures and epilepsy]. / Citocinas y sistema nervioso: relacion con crisis convulsivas y epilepsia.

INTRODUCTION. The immune system and the peripheral and central nervous system are in constant communication by means of messengers and signalling molecules released, such as cytokines, neuropeptides, neurohormones and neurotransmitters, among others. Seizures are defined as the transitory appearance of signs and symptoms that trigger an abnormally excessive neuronal activity in the brain. Following seizures the generation of a neuroinflammatory process has been observed to occur, with the consequent release of proinflammatory cytokines and inflammation-mediating molecules, which make the patient more prone to epilepsy. AIM. To offer evidence suggesting and supporting the role of cytokines in the appearance of seizures and in epilepsy, since these molecules have proven to have dual properties. DEVELOPMENT. The central nervous system, by means of the blood-brain barrier, restricts the flow of activated cells and inflammation mediators released from the peripheral system towards the brain parenchyma. Moreover, there is also another series of mechanisms that contributes to the 'selective and modified' immunity of the central nervous system. The purpose of all this series of events is to limit the responses of the immune system at central level, although it has been shown that in the central nervous system they are permanently under the control and regulation of the immune system. CONCLUSIONS. Cytokines in epilepsy play a dual role with pro- and anti-convulsive properties. Seizures do not induce the expression of cytokines only inside the brain, but also peripherally.

TITLE: Citocinas y sistema nervioso: relacion con crisis convulsivas y epilepsia.Introduccion. El sistema inmune y el sistema nervioso periferico y central se encuentran en constante comunicacion a traves de mensajeros y moleculas de señalizacion liberadas, como las citocinas, los neuropeptidos, las neurohormonas y los neurotransmisores, entre otros. Las convulsiones se definen como la aparicion transitoria de signos y sintomas que inducen una actividad neuronal excesiva anormal en el cerebro; despues de una crisis convulsiva, se ha observado la generacion de un proceso neuroinflamatorio, con la consecuente liberacion de citocinas proinflamatorias y de moleculas mediadoras de inflamacion, que predisponen a la epilepsia. Objetivo. Mostrar la evidencia que sugiere y apoya el papel de las citocinas en la aparicion de crisis convulsivas y en la epilepsia, ya que estas moleculas han demostrado propiedades duales. Desarrollo. El sistema nervioso central, a traves de la barrera hematoencefalica, restringe el flujo de celulas activadas y de mediadores de inflamacion liberados desde el sistema periferico hacia el parenquima cerebral; ademas, existe otra serie de mecanismos que contribuyen a la inmunidad 'selectiva y modificada' del sistema nervioso central. Toda esta serie de eventos tiene la finalidad de limitar respuestas del sistema inmune a nivel central, aunque se ha demostrado que en el sistema nervioso central se encuentran de manera permanente bajo el control y la regulacion del sistema inmune. Conclusiones. Las citocinas en la epilepsia muestran un papel dual con propiedades pro y anticonvulsionantes. Las convulsiones no solamente inducen la expresion de citocinas dentro del cerebro, sino tambien perifericamente.

Comparison between febrile and afebrile seizures associated with mild rotavirus gastroenteritis.

PURPOSE: We aimed on identifying the differences of febrile and afebrile seizures associated with mild rotavirus gastroenteritis (RVGE) in the pediatric population. METHOD: Medical charts of pediatric patients who had been admitted between July 1999 and June 2011 due to RVGE were retrospectively reviewed. Subjects were ultimately divided into three groups; 'no seizure' (NS: patients without seizure), 'febrile seizure' (FS: patients with fever during seizure), 'afebrile seizure' (AFS: patients without fever during seizure). Comparisons between groups were carried out on demographic and clinical characteristics, laboratory test results, electroencephalogram findings, brain magnetic resonance imaging findings, antiepileptic treatment, and prognosis. RESULTS: Among the 755 subjects who had been admitted due to mild rotavirus enteritis, 696 (90.3%) did not have any seizures, 17 (2.2%) had febrile seizures, 42 (5.5%) had afebrile seizures. The duration of gastrointestinal symptoms before the onset of seizures were significantly shorter in the FS group compared to the AFS group (1.3±0.8 vs. 2.8±1.0 days; p<0.0001). A single seizure attack was significantly higher in the AFS group (3.0±1.6 vs. 1.7±1.0 episodes; p=0.0003), and the frequency of seizures that were of focal type with or without secondary generalization were significantly higher in the AFS group (33.3% vs. 6.0%; p=0.0139). All patients among the FS and AFS group had not received further antiepileptic treatment after discharge, and none developed epilepsy during follow up period. CONCLUSION: Despite some differences in seizure characteristics, both febrile and afebrile seizures associated with mild RVGE were mostly benign with a favorable prognosis.

"Simple febrile seizures plus (SFS+)": more than one febrile seizure within 24 hours is usually okay.

This study aimed to investigate whether children with recurrent febrile seizures within a 24-hour period need to be worked up differently from children with simple febrile seizures. Inclusion criteria included the following: (i) children with first seizure cluster between 4 months and 3 years of age, (ii) children who had more than one febrile seizure within 24 hours, and (iii) children who returned to baseline between and after each event. Thirty-two patients met the inclusion criteria over a 3-year period. All patients underwent brain CT and/or MRI and EEG. All head CTs were normal. Two children had abnormal MRI findings - both benign: one is thought to represent postictal changes, and the other one is an incidental arachnoid cyst. Of the 4 abnormal EEGs, one showed epileptiform discharges, while the others showed generalized ictal or postictal features. We propose the term "simple febrile seizures plus (SFS+)" to describe children who have more than one seizure within 24 hours but who are otherwise not different in presentation from children with SFS.