Subsequent Epilepsy Research Articles

Are febrile seizures an indication for intermittent benzodiazepine treatment, and if so, in which cases?

Febrile seizures occur in ∼4% of children. After a first febrile seizure, the risk of recurrence is ∼40%, but excellent studies document that febrile seizures do not cause brain damage or deficits in cognition or behaviour. The risk of subsequent epilepsy is 2-4%. Prolonged febrile seizures are of concern because a child may later develop mesial temporal sclerosis and intractable epilepsy in rare cases. Most prolonged febrile seizures represent the first febrile seizure and cannot be anticipated. A first prolonged febrile seizure does not increase the risk of recurrence, but if there is a recurrence, it is more likely to be prolonged. Prevention of recurrent febrile seizures is difficult. Antipyretics are ineffective. Daily AED treatment is not often justified. Intermittent oral diazepam at the time of illness is not very successful and has significant side effects. The most optimistic study found that the number of subjects required to treat in order to prevent one recurrence was 14. Intermittent clobazam has fewer side effects than diazepam and may be somewhat effective. Rescue benzodiazepines given outside health care facilities may be effective in selected patients to prevent prolonged recurrences, although this has not been proven with rectal diazepam which has been more extensively studied than buccal or nasal midazolam. Currently, we suggest that, for children with febrile seizures, candidates for consideration for rescue benzodiazepines are those with a prolonged febrile seizure or poor access to medical care. It is possible that the use of a rescue benzodiazepine may alleviate severe parental anxiety, but this remains to be established.

Status Epilepticus and Subsequent Epilepsy

Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease.REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952.Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m2 (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1–5·9) comprising 51 820 person-years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77–0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68–0·87; p<0·0001), with HRs of 0·89 (0·78–1·01; p=0·066) for sustained decline in eGFR of 30% or more and 0·75 (0·39–1·44; p=0·39) for chronic renal replacement therapy.Long-term use of dulaglutide was associated with reduced composite renal outcomes in people with type 2 diabetes.Eli Lilly and Company.

Short-Term Exposure to Ambient Ozone and Acute Stroke Risk: A Case-Crossover Analysis

Short-Term Exposure to Ambient Ozone and Acute Stroke Risk: A Case-Crossover Analysis

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.

Transcriptome analysis of the hippocampus in novel rat model of febrile seizures.

Febrile seizures (FS) are the most common type of convulsive events in infants and young children, but the precise underlying genetic mechanism remains to be explored. To investigate the underlying pathogenic factors in FS and subsequent epilepsy, alterations in gene expression between the two new strains of rats (hyperthermia-prone [HP] vs hyperthermia-resistant [HR]), were investigated by using the Whole Rat Genome Oligo Microarray. This process identified 1,140 differentially expressed genes (DEGs; 602 upregulated and 538 downregulated), which were analyzed to determine significant Gene Ontology (GO) categories, signaling pathways and gene networks. Based on the GO analyses, the modified genes are closely related to various FS pathogenesis factors, including immune and inflammatory responses and ion transport. Certain DEGs identified have not been previously examined in relation to FS pathogenesis. Among these genes is dipeptidyl peptidase 4 (DPP4), a gene closely linked to interleukin 6 (IL-6), which played a key role in the gene network analysis. Furthermore, sitagliptin, a DPP4 inhibitor significantly decreased epileptic discharge in rats, observed via electroencephalogram, suggesting an important role for DPP4 in FS. The effectiveness of sitagliptin in reducing seizure activity may occur through a mechanism that stabilizes cellular Ca2+ homeostasis. In addition, DPP4 expression may be regulated by DNA methylation. The hippocampal gene expression profiles in novel rat models of FS provides a large database of candidate genes and pathways, which will be useful for researchers interested in disorders of neuronal excitability.

Long-term follow-up in children with benign convulsions associated with gastroenteritis

BackgroundThe outcome of benign convulsions associated with gastroenteritis (CwG) has generally been reported as being excellent. However, these data need to be confirmed in studies with longer follow-up evaluations. AimTo assess the long-term neurological outcome of a large sample of children presenting with CwG. MethodsWe reviewed clinical features of 81 subjects presenting with CwG (1994–2010) from three different Italian centers with a follow-up period of at least 3 years. ResultsFollow-up period ranged from 39 months to 15 years (mean 9.8 years). Neurological examination and cognitive level at the last evaluation were normal in all the patients. A mild attention deficit was detected in three cases (3.7%). Fourteen children (17.3%) received chronic anti-epileptic therapy. Interictal EEG abnormalities detected at onset in 20 patients (24.7%) reverted to normal. Transient EEG epileptiform abnormalities were detected in other three cases (3.7%), and a transient photosensitivity in one (1.2%). No recurrence of CwG was observed. Three patients (3.7%) presented with a febrile seizure and two (2.5%) with an unprovoked seizure, but none developed epilepsy. ConclusionsThe long-term evaluation of children with CwG confirms the excellent prognosis of this condition, with normal psychomotor development and low risk of relapse and of subsequent epilepsy.

Risk Factors for Epilepsy after Febrile Seizures

Investigators from Aristotle University of Thessaloniki, Greece, identified prognostic factors for subsequent epilepsy in a prospective study of 501 children with a first febrile seizure (FS).

Epileptiform Discharges and Frontal Paroxysmal EEG Abnormality Act as Predictive Marker for Subsequent Epilepsy in Children With Complex Febrile Seizures

Using electroencephalography (EEG) for diagnosing subsequent epilepsy in children after febrile seizure (FS) is not common. The present study investigates the relationship between epileptiform discharges and subsequent epilepsy, and looks for the predictive marker for this disorder. A total of 378 children with complex FS and whose EEG showed epileptiform discharges or normal EEG were included. Development of FS was compared between those with epileptiform discharges and those with normal EEG. Risk factors were analyzed using multivariate logistic regression to clarify their effects on subsequent epilepsy. The association between generalized or focal EEG localization, and between frontal epileptiform discharges and subsequent epilepsy, were analyzed. Among 378 patients with complex FS, 51 showed epileptiform discharges. History of epilepsy, frontal seizure, number of FS, and prolonged seizure were the risk factors for epileptiform discharge. Subsequent epilepsy was significantly frequent in patients with more than 2 risk factors (odds ratio [OR] = 17; 95% confidence interval [CI] = 4.1-29.6). Prolonged seizure (OR = 4.98; 95% CI = 1.63-13.29), FS number (OR = 2.96; 95% CI = 1.23-10.51), and family history of epilepsy (OR = 2.67; 95% CI = 1.05-7.63) were significantly correlated with subsequent epilepsy. Of 9 patients with paroxysms in the frontal region, 8 (88.9%) developed epilepsy. There was concordance between frontal epileptiform discharges and subsequent epilepsy (κ = .901). In conclusion, epileptiform discharges are risk factors for subsequent epilepsy. Frontal paroxysmal EEG is a marker for subsequent epilepsy.

Febrile seizures.

Febrile seizure (FS) is the most common seizure disorder of childhood, and occurs in an age-related manner. FS are classified into simple and complex. FS has a multifactorial inheritance, suggesting that both genetic and environmental factors are causative. Various animal models have elucidated the pathophysiological mechanisms of FS. Risk factors for a first FS are a family history of the disorder and a developmental delay. Risk factors for recurrent FS are a family history, age below 18 months at seizure onset, maximum temperature, and duration of fever. Risk factors for subsequent development of epilepsy are neurodevelopmental abnormality and complex FS. Clinicians evaluating children after a simple FS should concentrate on identifying the cause of the child's fever. Meningitis should be considered in the differential diagnosis for any febrile child. A simple FS does not usually require further evaluation such as ordering electroencephalography, neuroimaging, or other studies. Treatment is acute rescue therapy for prolonged FS. Antipyretics are not proven to reduce the recurrence risk for FS. Some evidence shows that both intermittent therapy with oral/rectal diazepam and continuous prophylaxis with oral phenobarbital or valproate are effective in reducing the risk of recurrence, but there is no evidence that these medications reduce the risk of subsequent epilepsy. Vaccine-induced FS is a rare event that does not lead to deleterious outcomes, but could affect patient and physician attitudes toward the safety of vaccination.

Caregivers' Knowledge, Concerns and Management of Pediatric Febrile Convulsions.

PURPOSE: The purpose of this study was to investigate caregivers' knowledge, concerns, and management of children with febrile convulsions (FC).METHODS: A descriptive correlation study was conducted with 133 caregivers whose children had been diagnosed with a FC.A self-administered questionnaire was used for data collection. Descriptive statistics, t-test, one-way analysis of variance and Pearson's correlation were used for data analysis.RESULTS: The mean percent of correct answers related to knowledge was 48.5%. Many caregivers believed that FC causes brain damage and did not know that risk of subsequent epilepsy in FC is rare. Levels of concern about FC were high. Caregivers were highly concerned about further FC attacks in the night and tended to worry that Febrile children were apt to get a fever. Many caregivers used management practices which are not recommended for FC in children. There was a statistically significant negative correlation between caregivers' knowledge and concerns about FC. There was also a positive correlation between caregivers' knowledge and management of FC.CONCLUSION: Findings suggest that improvements are needed in caregivers' knowledge and management of FC. Caregivers' concerns related to misconception need to be addressed.Development and evaluation of educational interventions on changing caregivers' management of FC are recommended.

Prognostic factors for subsequent epilepsy in children with febrile seizures

Epilepsy following febrile seizures (FS) has been estimated between 2% and 7%. It concerns a prospective study in a large sample of children with a long-term follow-up. The aim of this study is to identify the prognostic factors that can lead children with FS to epilepsy. Children with a first episode of FS were included. We gathered information about prenatal and perinatal history, family history of FS and epilepsy in first- and second degree relatives, age at the time of the initial FS, dates of FS recurrences, focality, duration of the FS and recurrent episodes within the same febrile illness, height and duration of fever prior to the seizure, cause of the fever, and frequency of febrile illnesses. Patients were seen every 4-6months and also at each recurrence. A group of 560 children with a first FS met all entry criteria. Epilepsy was recorded at 5.4%. Statistical analysis was performed between children with epilepsy and those with no afebrile seizure. We analyzed FS recurrences in accordance with the occurrence of epilepsy. From the third FS recurrence and beyond, only focality continued to have prognostic value. Main prognostic factors for the development of epilepsy after FS are: (1) complex FS that increased the risk for epilepsy 3.6 times, (2) age at onset of FS beyond the third year of life that raised the risk 3.8 times, (3) positive family history of epilepsy 7.3 times, and (4) multiple episodes of FS about 10 times. Focality at the first and the second FS recurrence increased the risk of epilepsy about 9.7 and 11.7 times, respectively. Focality was the only factor that continued to be significant in further FS recurrences. A prognostic profile of each child with FS would be very useful for the follow-up of these children.

Risks of subsequent epilepsy among patients with hypertensive encephalopathy: A nationwide population-based study

BackgroundTo determine whether the diagnosis of hypertensive encephalopathy (HE) is linked to an increased risk of subsequent epilepsy by using a nationwide population-based retrospective study. MethodsOur study featured a study cohort and a comparison cohort. The study cohort consisted of all patients with newly diagnosed HE between 1997 and 2010, compiled from universal insurance claims data on patients with hypertension taken from the National Health Insurance Research Database. The comparison cohort comprised the remaining hypertensive patients without encephalopathy. The follow-up period was terminated following the development of epilepsy, death, withdrawal from the National Health Insurance system, or the end of 2010. We determined the cumulative incidences and hazard ratios (HRs) of epilepsy development. ResultsThe incidence of subsequent epilepsy was 2.25-fold higher in the patients with HE than in comparisons (4.17 vs. 1.85 per 1000person-years), with an adjusted HR of 2.06 (95% CI=1.66–2.56) in the multivariable Cox proportional-hazards regression analysis. The incidence of epilepsy was higher in men, younger patients with HE, and those with brain disorders. ConclusionsWe found that, in Taiwan, patients with HE are at an increased risk of subsequent epilepsy. Physicians should be aware of HE's link to epilepsy when assessing patients with HE.

Autosomal recessive mutations in nuclear transport factor KPNA7 are associated with infantile spasms and cerebellar malformation

Nuclear import receptors of the KPNA family recognize the nuclear localization signal in proteins and together with importin-β mediate translocation into the nucleus. Accordingly, KPNA family members have a highly conserved architecture with domains that contact the nuclear localization signal and bind to importin-β. Here, we describe autosomal recessive mutations in KPNA7 found by whole exome sequencing in a sibling pair with severe developmental disability, infantile spasms, subsequent intractable epilepsy consistent with Lennox-Gastaut syndrome, partial agenesis of the corpus callosum, and cerebellar vermis hypoplasia. The mutations mapped to exon 7 in KPNA7 result in two amino-acid substitutions, Pro339Ala and Glu344Gln. On the basis of the crystal structure of the paralog KPNA2 bound to a bipartite nuclear localization signal from the retinoblastoma protein, the amino-acid substitutions in the affected subjects were predicted to occur within the seventh armadillo repeat that forms one of the two nuclear localization signal-binding sites in KPNA family members. Glu344 is conserved in all seven KPNA proteins, and we found that the Glu354Gln mutation in KPNA2 is sufficient to reduce binding to the retinoblastoma nuclear localization signal to approximately one-half that of wild-type protein. Our data show that compound heterozygous mutations in KPNA7 are associated with a human neurodevelopmental disease, and provide the first example of a human disease associated with mutation of a nuclear transport receptor.

A new locus for familial temporal lobe epilepsy on chromosome 3q

Temporal lobe epilepsy (TLE) is a common and heterogeneous focal epilepsy syndrome with a complex etiology, involving both environmental and genetic factors. Several familial forms of TLE have been described, including familial lateral TLE (FLTLE), familial mesial TLE (FMTLE) without hippocampal sclerosis, and FMTLE with hippocampal sclerosis. Mutations have been identified only in the leucine-rich, glioma-inactivated 1 (LGI1) gene on chromosome 10q22-q24 in FLTLE. Several loci have been mapped in families with FMTLE, but responsible genes have not been found. We report clinical evaluation in a large family with FMTLE and a new genetic locus. We conducted a genome-wide scan using 10cM-spaced microsatellite markers on a family with TLE. Seven individuals had TLE without antecedent FS; four other individuals had FS during childhood, but no subsequent epilepsy. Patients with TLE had infrequent simple partial, complex partial and secondarily generalized seizures that generally responded well to treatment. The proband had no hippocampal sclerosis. The mode of inheritance appeared to be autosomal dominant with incomplete penetrance. Linkage analysis was performed using the Genehunter software. Regions with LOD score>1 and those that were poorly informative in the first-pass scan were further genotyped. Linkage was identified on chromosome 3q25-q26 in a 13cM region flanked by markers D3S1584 and D3S3520, with a peak LOD score of 3.23. This interval does not correspond to any previously known locus for familial epilepsy or FS. KCNAB1, encoding a voltage-gated, shaker-related potassium channel, and NLGN1, encoding a member of a family of neuronal cell surface protein were excluded as disease causing mutations. We identified a novel locus for familial TLE with FS, providing additional evidence of the complexity and genetic heterogeneity of familial focal epilepsy.

Pediatric Seizures

On the basis of strong evidence, treatment is highly dependent on the seizure semiology results, electroencephalography (EEG) findings, and origin. • On the basis of moderate evidence and consensus, vigorous use of video EEG recordings and home video cameras should be used to delineate the epileptic syndromes. • On the basis of strong evidence, pediatric epilepsy syndromes have common comorbidities. As a consensus, some pediatric epilepsy centers consider referral to a neuropsychologist to be first-line care in these patients. • On the basis of strong evidence and consensus, antiepileptic drug therapy has its own complications and should be discontinued after an appropriate treatment course. • On the basis of moderate evidence and consensus, uncontrolled seizures put patients at risk for significant morbidity and mortality.

Febrile seizures: recent developments and unanswered questions

Febrile seizures (FS) are typically observed in infants and children affecting 2-5% of the pediatric population and are the commonest seizures in childhood. The present review summarizes epidemiology, etiology, clinical picture, and diagnostic procedures as well as the therapeutic options and the different courses this disorder may take. An extensive review of literature is performed, while views and aspects towards the pathogenesis of FS are stated. Risk factors for multiple recurrences of FS and for subsequent epilepsy are analyzed. Questions regarding the treatment and follow-up of children with FS are answered. Whereas the frequency of epilepsy following simple FS is estimated to be 1.0-2.2% of patients, and thus does not differ from the risk of normal population, complicated FS are associated with an increased risk of subsequent epilepsy in 4.1-6.0%. Febrile status epilepticus with focal symptoms may result in approximately 5% of cases in complex partial epilepsy. Furthermore, multiple recurrences increase the risk for generalized epilepsy (>4%). The immediate management of FS, intermittent prophylaxis, and the effectiveness of the treatment in combination with antipyretics are presented in detail. FS can cause a great anxiety and even panic to parents and to the whole family. Parents should be educated about the benign condition and the good prognosis. Although much information has been gained, much remains to be learned.

Treatment of infantile spasms.

Infantile spasms (West's Syndrome) is a syndrome that includes a peculiar type of epileptic seizure-the spasms-and an electroencephalographic (EEG) abnormality often called hypsarrhythmia. Psychomotor retardation is frequently found at follow-up. Approximately two-thirds of affected infants will have a detectable underlying neurological abnormality, but still little is known about the pathophysiological basis for infantile spasms, and treatment remains problematic. To compare the effects of single pharmaceutical therapies used to treat infantile spasms in terms of control of the spasms, resolution of the EEG, relapse rates, psychomotor development, subsequent epilepsy, side effects, and mortality. To identify published data, we searched the Cochrane Epilepsy Group Specialised Register (October 2012), CENTRAL (The Cochrane Library 2012, Issue 9), MEDLINE (1946 to September Week 4, 2012), EMBASE (1980 to March 2003), and the reference lists of all retrieved articles.To identify unpublished data, we searched the ISRCTN Register (www.controlled-trials.com), corresponded with colleagues and drug companies, and made requests at international conferences. All randomised controlled trials (RCTs) of the administration of drug therapy to patients with infantile spasms. Data collection from all relevant publications was independently undertaken by three review authors (before 2010) or by two review authors using a standard proforma. Analysis included assessment of study quality and a search for sources of heterogeneity. We found 16 small RCTs (fewer than 100 patients enrolled) and 2 larger RCTs (more than 100 patients enrolled). These 18 studies looked at a total of 916 patients treated with a total of 12 different pharmaceutical agents. Overall methodology of the studies was poor, in part because of ethical dilemmas such as giving placebo injections to children. Two studies showed that placebo was not as good as active treatment in resolving the spasms. The strongest evidence suggested that hormonal treatment (prednisolone or tetracosactide depot) leads to resolution of spasms faster and in more infants than does vigabatrin. Responses without subsequent relapse may be no different. The same study suggests that hormonal treatments might improve the long-term developmental outcome compared with vigabatrin in infants not found to have an underlying cause for their infantile spasms. To date, few well-designed RCTs have considered the treatment of infantile spasms, and the numbers of patients enrolled have been small. In the majority, methodology has been poor, hence it is not clear which treatment is optimal in the treatment of this epilepsy syndrome. Hormonal treatment resolves spasms in more infants than vigabatrin, but this may or may not translate into better long-term outcomes. If prednisolone or vigabatrin is used, high dosage is recommended. Vigabatrin may be the treatment of choice in tuberous sclerosis. Resolution of the EEG features may be important, but this has not been proven. Further research using large studies with robust methodology is required.

Predictors of Surgical Candidacy in 414 Epilepsy Patients Admitted to the EMU

Admission to an Epilepsy Monitoring Unit (EMU) is essential for pre-surgical evaluation of patients with medically-refractory epilepsy; however, prolonged referral times and resource limitations are significant access barriers. Therefore, identification of pre-EMU variables that predict potential surgical candidates can assist in the triage of patient admissions to the EMU. In this hypothesis-generating study, a retrospective analysis of patients admitted for pre-surgical evaluation to the Toronto Western Hospital EMU (2004-2011) was performed. Univariate and multivariate logistic regression was used to identify variables that could independently predict subsequent surgical candidacy following EMU evaluation. Four hundred and fourteen patients were admitted to the EMU. Overall, 259 patients (62.5%) were identified as potential surgical candidates. One hundred and seven patients (25.8%) required invasive electroencephalogram (iEEG) implantations; of 75 patients consenting to iEEG analysis 39 underwent a subsequent resective procedure. Male patients and those with a lesion on MRI were 1.9 times more likely to be surgical candidates (95% CI 1.18-2.98 and 0.94-3.80, respectively), while patients with non-localizable seizures were seven times less likely (95% CI 0.02-1.25). In this retrospective, hypothesis-generating study male gender, presence of a lesion on MRI and localizable seizures on routine outpatient EEG analysis independently predicted subsequent resective epilepsy surgical candidacy in EMU patients. Upon validation by other studies, these variables may be considered by clinicians referring patients to the EMU in order to improve wait times and optimize patient care.

Alteration of synaptic plasticity by neonatal seizures in rat somatosensory cortex

Seizures in newborns are associated with a high risk for subsequent epilepsy and adverse neurodevelopmental consequences. Understanding the mechanisms by which neonatal seizures adversely disturb the immature brain is important in developing therapeutic strategies. Using the convulsant agent flurothyl to mimic repetitive neonatal seizures we show that early-life seizures result in long-term alteration in the maintenance phase of long-term potentiation (LTP) in layer IV to layer II/III synapses of the somatosensory cortex without alteration of basal synaptic transmission, the induction phase of LTP and short-term depression. Such alterations may have a role in functional deficits seen following neonatal seizures.

Clinical and EEG risk factors for subsequent epilepsy in patients with complex febrile seizures

To identify the risk factors for subsequent epilepsy in patients with complex febrile seizures from a single-center retrospective cohort. The medical records of 1091 patients discharged with a diagnosis of febrile seizures from the Seoul National University Bundang Hospital from February 2004 to October 2009 were reviewed. One hundred eighty-three patients (107 boys and 76 girls) with complex febrile seizures who showed normal neurocognitive development were included in the analysis. Clinical characteristics, including features of complex febrile seizure, initial interictal electroencephalographic findings, and subsequent epilepsy, were reviewed and the odds ratio of subsequent epilepsy was estimated. The mean follow-up duration for subsequent epilepsy was 6.1 years (range, 2.5-8.0 years). Complex febrile seizures were observed in 22.6% of all patients with febrile seizures. Among 183 patients with complex febrile seizures, 22 patients (12.0%) developed subsequent epilepsy. Prolonged (>10 min) seizure (p=0.031; odds ratio, 3.04; 95% confidence interval, 1.11-8.32) or the presence of multiple seizures for 24 h (p=0.032; odds ratio, 3.63; 95% confidence interval, 1.12-11.8) was significantly more frequent in patients with subsequent epilepsy, whereas the presence of focal seizure was not significantly different. Epileptiform discharges (focal in all cases) were significantly more frequent in patients with subsequent epilepsy (50% vs. 13%, p=0.002), with an odds ratio of 5.15 (95% confidence interval, 1.84-14.5). The presence of epileptiform discharges is a significant risk factor for subsequent epilepsy in patients with complex febrile seizures. Electroencephalography should be considered in all patients with complex febrile seizures especially those who had multiple or prolonged seizures.