Partial Epilepsy Of Childhood Research Articles

ZFHX3 variants cause childhood partial epilepsy and infantile spasms with favourable outcomes

BackgroundThe ZFHX3 gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between ZFHX3 variants and epilepsy.MethodsWhole-exome sequencing was...

CELSR1 variants are associated with partial epilepsy of childhood.

CELSR1 gene, encoding cadherin EGF LAG seven-pass G-type receptor 1, is mainly expressed in neural stem cells during the embryonic period. It plays an important role in neurodevelopment. However, the relationship between CELSR1 and disease of the central nervous system has not been defined. In this study, we performed trios-based whole-exome sequencing in a cohort of 356 unrelated cases with partial epilepsy without acquired causes and identified CELSR1 variants in six unrelated cases. The variants included one de novo heterozygous nonsense variant, one de novo heterozygous missense variant, and four compound heterozygous missense variants that had one variant was located in the extracellular region and the other in the cytoplasm. The patients with biallelic variants presented severe epileptic phenotypes, whereas those with heterozygous variants were associated with a mild epileptic phenotype of benign epilepsy with centrotemporal spikes (BECTS). These variants had no or low allele frequency in the gnomAD database. The frequencies of the CELSR1 variants in this cohort were significantly higher than those in the control populations. The evidence from ClinGen Clinical-Validity Framework suggested a strong association between CELSR1 variants and epilepsy. These findings provide evidence that CELSR1 is potentially a candidate pathogenic gene of partial epilepsy of childhood.

Magnetic Resonance Imaging Findings and Their Association with Electroencephalogram Data in Children with Partial Epilepsy.

BackgroundIt is important to identify the neuroimaging features that are associated with partial epilepsy in children. Advances in technology have recently been made to localize focal epileptogenic lesions, especially high-resolution structural imaging with magnetic resonance imaging (MRI). The recommendation that electroencephalography (EEG) should be the gold standard and that MRI should be optional has been questioned. The present study aims to evaluate the efficacy of MRI in children with partial epilepsy and to compare the diagnostic yields of MRI and EEG data.MethodsThe present study was conducted among one hundred twelve 1- to 6-year-old children with partial epilepsy. All patients underwent EEG and brain MRI. The epileptogenic lesions were identified on the basis of the signal intensities and morphological abnormalities seen on MRI. The correlation between MRI and EEG abnormal findings was analyzed using a chi-square test.ResultsAbnormal MRI findings were present in 34.8% (n = 39) of the sample. The EEG and MRI data agreed with respect to classifications into abnormal or normal in 48.2% of the sample (n = 54). Of the 27 patients with normal EEG findings, six (22.2%) had abnormal MRI findings. Inter-rater agreement showed the compatibility between EEG and MRI not significant (weighted Kappa = 0.105).ConclusionA number of MRI abnormalities were found in our study of otherwise normal children, although the correlation between these results was not clear. The follow-up of these children will help us identify the important abnormalities. Despite the small sample size, our results showed that normal EEG findings do not predict normal brain MRI data in children with partial epilepsy.

Pharmacoresistant Atypical Benign Partial Epilepsy of Childhood: Early Introduction of Specific Therapies to Prevent Cognitive Decline

AbstractAtypical benign partial epilepsy (ABPE) of childhood is a special type of epileptic syndrome characterized by the combination of epileptic negative myoclonus, atypical absence seizures, focal motor seizures, and a continuous spike–wave during slow sleep (CSWS). Although the seizures are resistant to antiseizure drugs (ASDs) effective for focal epilepsy, they are markedly responsive to ethosuximide (ESM). An incorrect ASD choice may aggravate the seizures and CSWS, resulting in a pseudo-catastrophic state or nonconvulsive status epilepticus. In this study, we retrospectively investigated the effectiveness of steroid and ketogenic diet (KD) therapies for children with ABPE resistant to ASDs, including ESM. Adrenocorticotropic hormone (ACTH) therapy (n = 4), KD therapy (n = 4), and an oral steroid (n = 2) were tried for eight patients (two patients tried two therapies). An excellent response (seizure-free period > 1 year) was achieved by four out of four patients undergoing ACTH therapy, two out of four undergoing KD therapy, and one out of two receiving oral steroid therapy. In conclusion, steroid and KD therapies are reasonable treatment options early in the course of treatment of children with pharmacoresistant ABPE to prevent a decline in cognitive function due to the persistence of epileptic encephalopathy. The majority of patients in our case series had an excellent response, though further studies are warranted to confirm their efficacy and safety.

Atypical Benign Partial Epilepsy of Childhood Treated with Prednisolone and Ethosuximide

Atypical Benign Partial Epilepsy of Childhood Treated with Prednisolone and Ethosuximide

PND1 - Meta-Analysis of Newer Anti-Epileptic Drugs for Treatment of Partial Epilepsy in Children

PND1 - Meta-Analysis of Newer Anti-Epileptic Drugs for Treatment of Partial Epilepsy in Children

Long-Term Clinical and Electroencephalography (EEG) Consequences of Idiopathic Partial Epilepsies.

BackgroundIdiopathic partial epilepsies of childhood (IPE) affect a considerable proportion of children. Three main electroclinical syndromes of IPE are the Benign Childhood Epilepsy with Centro-temporal Spikes (BECTS), Panayiotopoulos Syndrome (PS), and Childhood Epilepsy with Occipital Paroxysms (CEOP). In this study we investigated the long-term prognosis of patients with IPE and discussed the semiological and electroencephalography (EEG) data in terms of syndromic characteristics.Material/MethodsThis study included a group of consecutive patients with IPE who had been followed since 1990. Demographic and clinical variables were investigated. Patients were divided into 3 groups – A: Cases suitable for a single IPE (BECTS, PS and CEOP); B: cases with intermediate characteristics within IPEs; and C: cases with both IPE and IGE characteristics. Long-term data regarding the individual seizure types and EEG findings were re-evaluated.ResultsA total of 61 patients were included in the study. Mean follow-up duration was 7.8±4.50 years. The mean age at onset of seizures was 7.7 years. There were 40 patients in group A 40, 14 in group B, and 7 in group C. Seizure and EEG characteristics were also explored independently from the syndromic approach. Incidence of autonomic seizures is considerably high at 2–5 years and incidence of oromotor seizures is high at age 9–11 years. The EEG is most abnormal at 6–8 years. The vast majority (86%) of epileptic activity (EA) with parietooccipital is present at 2–5 years, whereas EA with fronto-temporal or multiple sites become more abundant between ages 6 and 11.ConclusionsResults of the present study provide support for the age-related characteristics of the seizures and EEGs in IPE syndromes. Acknowledgement of those phenomena may improve the management of IPEs and give a better estimate of the future consequences.

PSEUDO-LENNOX SYNDROME: CLINICAL AND ELECTROENCEPHALOGRAPHIC CHARACTERISTICS

Pseudo-Lennox syndrome (PLS), or atypical benign partial epilepsy of childhood, is a disease from a group of age-related epileptic encephalopathies with a phenomenon of continuous spike-wave activity during slow sleep, which manifests itself as frequent polymorphic focal motor and pseudogeneralized seizures, cognitive impairments, as well as regional and diffuse epileptiform activity on electroencephalogram (EEG) by the morphology identical to that of benign epileptiform patterns of childhood. The disease was first described by J. Aicardi and J. J. Chevrie in 1982, based on a study of 7 cases. Its diagnostic complexity is the polymorphism of both epileptic seizures and EEG data, as well as low awareness of the syndrome among physicians and its absence in the international classification of epilepsies. The typical triad of seizures, which occurs in nearly 100 % of patients, encompasses focal motor paroxysms (identical to those as observed in Rolandic epilepsy), atypical absences, and atonic seizures. Seizures in PLS in its active period (generally up to 7–8 years) are highly resistant to antiepileptic drugs. Only a few agents have been proven to be effective in PLS; these include valproates, succinimides, benzodiazepines, topiramate, and sulthiame. The frequency of seizures are noted to increase in patients with PLS treated with drugs, such as vigabatrin, gabapentin, lamotrigine, phenobarbital, or phenytoin. The author considers in detail the history of studies of the disease, clinical manifestations, diagnostic criteria, therapeutic approaches, and prognosis.

Atypical benign partial epilepsy of childhood with acquired neurocognitive, lexical semantic, and autistic spectrum disorder.

Atypical benign partial epilepsy (ABPE) of childhood or pseudo-Lennox syndrome is a form of idiopathic focal epilepsy characterized by multiple seizure types, focal and/or generalized epileptiform discharges, continuous spike–wave during sleep (CSWS), and sometimes reversible neurocognitive deficits. There are few reported cases of ABPE describing detailed correlative longitudinal follow-up of the various associated neurocognitive, language, social communicative, or motor deficits, in parallel with the epilepsy. Furthermore, the molecular inheritance pattern for ABPE and the wider spectrum of epilepsy aphasia disorders have yet to be fully elucidated. We describe the phenotype–genotype study of a boy with ABPE with follow-up from ages 5 to 13 years showing acquired oromotor and, later, a specific lexical semantic and pervasive developmental disorder. Exome sequencing identified variants in SCN9A, CPA6, and SCNM1. A direct role of the epilepsy in the pathogenesis of the oromotor and neurocognitive deficits is apparent.

Pseudo Lennox syndrome: experience of hormone therapy application

Atypical partial epilepsy of childhood or the pseudo - Lennox syndrome is a disease leading to cognitive, speech and motor disorders that impair adaptation and complicates the therapy. Many patients with different forms of epilepsy resistant to conventional drug treatments. Hormone therapy is an alternative method of treatment pseudo - Lennox syndrome conducive to the correction of epileptic seizures and decrease regression of child development. This article describes a clinical case of successful hydrocortisone application in treatment of the pseudo-Lennox syndrome in 5 years old boy. Described the used scheme of treatment and reflects the dynamics of clinical process. The result of this treatment was the relief of the status of atypical absence seizures and reduce symptoms of oro-linguo- buccomotory dyspraxia.

1-A-D-10. A study on spike focus-dependence of high-frequency oscillations in benign childhood partial epilepsy

We analyzed spike-associated high-frequency oscillations (HFOs) and their relationship to spike foci in electroencephalograms (EEGs) of patients with benign epilepsy with centrotemporal spikes (BECTS) and Panayiotopoulos syndrome (PS). In 35 patients with BECTS and 29 with PS, focal spikes in scalp sleep EEGs were firstly classified into clusterings according to their characteristics including shapes and distributions. In each patient, the maximum of three spike clusters were investigated through time–frequency and single-dipole analyses to explore relationships between presence or absence of spike-associated HFOs and the distribution of estimated spike sources. A total of 159 spike clusters was analyzed (96 in BECTS and 63 in PS). HFOs were detected in 73 spike clusters (76.0%) in BECTS and 37 (58.7%) in PS with a statistically significant difference ( p = 0.024 by Fisher’s exact test). In BECTS, the spike sources had a close relationship with HFOs and were largely uniform irrespective of presence or absence of HFOs. In contrast in PS, the spikes tended to be dispersed and the rate of association with HFOs was significantly higher in occipito-parietal spikes (29/39) than the others (8/24; p = 0.002) suggesting that occipito-parietal spikes with a close link to HFOs were indicated to have a particular meaning in the epileptogenesis.

The genetic research progress in benign childhood epilepsy with centro-temporal spikes

Benign epilepsy with centro-temporal spikes(BECT)is the most common epilepsy syndrome in childhood.The seizures are manifested with facial jerking and twitching to guttural noises, salivating with inability to speak and twitched limbs.The episode is proved to be closely associated with sleep, especially the non-rapid eye movement period.Centrotemporal spikes are the hallmark of the syndrome of BECT.Although the pathogenesis of BECT is still unknown, it is generally acknowledged that hereditary features play a critical role in the occurrence of BECT.In this article we are going to summarize the progresses of BECT in the fields of clinical genetics, cytogenetics and molecular genetics. Key words: Benign partial epilepsy of childhood with centro-temporal spikes; Genetics; Epilepsy

Treatment of pediatric epilepsy in Poland

BackgroundThe many types of childhood epilepsies make the diagnosis and treatment difficult and the outcomes frequently poor. Furthermore, there are few clinical trials in pediatric epilepsy that provide useful results to guide daily practice. Therefore for pediatric neurologists expert opinion may be useful. AimsTo provide an overview of current practice in Poland and compare results with European and US clinical guidelines. MethodsPolish specialists in pediatric neurology were asked to participate in a survey about pediatric epilepsy. The focus of the questions was on the overall strategy and treatment options for different syndromic diagnoses. The survey was developed and performed according to a previous European survey (Wheless et al., 2007). ResultsFifty-one Polish specialists, working in academic or clinical settings, completed the questionnaire. They limited combination therapy to two or three antiepileptic drugs. Valproate was the treatment of choice for myoclonic, generalized tonic-clonic seizures and Lennox-Gastaut syndrome. For infantile spasms caused by tuberous sclerosis and of symptomatic etiology, vigabatrin was treatment of choice; valproate and ACTH were other first line options. Valproate and ethosuximide were chosen for childhood absence epilepsy and valproate for juvenile absence epilepsy. Carbamazepine was the first-line treatment option for benign partial epilepsy of childhood with centrotemporal spikes and complex partial seizures. In the treatment of juvenile myoclonic epilepsy for males valproate, for females lamotrigine were chosen. ConclusionPolish pediatric neurologists agreed on the majority of questions. Their views reflect the clinical utility and availability of treatment options in Poland. Results may provide direction for clinicians.

Prevalence of Celiac Disease in Children With Idiopathic Epilepsy in Southeast Turkey

BackgroundWe examined the prevalence of celiac disease in children with idiopathic epilepsy. MethodsPatients were screened for celiac disease using the immunoglobulin A anti-tissue transglutaminase antibody. Upper gastrointestinal endoscopy and small intestinal biopsy were offered to all antibody-positive patients. The control group consisted of 400 healthy children. ResultsA total of 600 patients (332 boys, 268 girls; 8 months-15 years; 9.40 ± 4.09 years) were studied. In 38 patients, the diagnosis was childhood partial epilepsy with occipital paroxysms. Six of the 38 patients with childhood partial epilepsy with occipital paroxysms (15.7%) had positive immunoglobulin A anti-tissue transglutaminase antibody. The frequency of biopsy-proven celiac disease was 15.7% (6/38) among children with childhood partial epilepsy with occipital paroxysms. None of the control patients had positive immunoglobulin A anti-tissue transglutaminase antibody results. ConclusionsThese findings suggest that the prevalence of celiac disease in children with partial epilepsy with occipital paroxysms may be higher than with other types of epilepsies. It may be reasonable to screen individuals with this type of epilepsy for celiac disease.

Clinical characteristics and outcome of children with electrical status epilepticus during slow wave sleep.

Background:Electrical status epilepticus in slow wave sleep (ESES) is a rare, age-related, self-limited disorder characterized as epilepsy with different seizure types, neuropsychological impairment in the form of global or selective regression of cognitive functions, motor impairment, and typical electroencephalographic (EEG) findings of continuous epileptic activity occupying 85% of nonrapid eye movement sleep.Aims:The aim is to examine the clinical and electrophysiological findings and treatment modalities of children with ESES and to evaluate the outcome of the disorder.Materials and Methods:Fourteen patients with a diagnosis of electrical status epilepticus during slow wave sleep and followed-up at least 2 years were included.Statistical Analysis:Pearson correlation test was used in the study.Results:Among the 14 patients, eight of them had normal mental development before ESES. Twelve of the patients mentioned cognitive impairment and decline in school performance during ESES. After ESES, seven patients had mental retardation in different severity. One of these patients was diagnosed with benign partial epilepsy of childhood with centrotemporal spikes and had normal intelligence quotient level prior to ESES. The diagnosis of ESES was made after newly occurred different seizure types in four of the patients while two of the previously known epileptic patients presented with only severe psychiatric impairment. Valproic acid and carbamazepine were the mostly frequently used drugs before the onset of ESES. After at least 2 years of follow-up, seven patients were seizure free, but still taking antiepileptic treatment. Five patients were seizure free, while two of them had ongoing seizures despite antiepileptic therapy.Conclusion:ESES should be kept in mind in children with unexplained regression or stagnation of development associated with seizures or not. Sleep EEGs should be performed for timely diagnosis, proper treatment and prevention of permanent cognitive impairment.

The penelope syndrome not always means bad prognosis

Introduction Penelope spun during the day and undid it during the night so, which the brain makes during the day, is erased during the night by the epileptic activity. The epileptic syndromes with continuous spike-wave during slow sleep (CSWS) are a group of authentic epileptic encephalopathies and show a wide clinical spectrum with common characteristics that includes the increase and generalization of epileptifrom discharges in the EEG during sleep. In addition, patients have neuropsychological disturbances, including aphasia. The onset of these syndromes is around 4 or 5 years of age and stabilize or even improve around puberty. It is a rare syndrome that occurs exclusively in childhood, with a variable etiology. Prognosis is influenced by the age of onset and the persistence over the time of the CSWSS pattern, being worse in cases in which this abnormality appears at early ages and longer permanence. Materials and methods We report two cases of children with CSWS pattern but with different clinical presentations. Results The first one is a 6 years aged girl with a diagnosis of benign epilepsy of childhood, who changes her seizures pattern and starts to have delay in the school, showing a CSWS in the sleep EEG. She was diagnosed of atypical benign partial epilepsy of childhood, treated, with a good outcome (disappearance both seizures and CSWS pattern). This case would be the benign side of the CSWS encephalopathies spectrum. The second one is a case of a sudden acquired aphasia when the patient was 6 years old, who never suffered epileptic seizures, but shows a CSWS pattern in the EEG. He was diagnosed of Landau–Kleffner syndrome, trated with antiepileptics drugs and corticosteroids, with a benign clinical course (language recovering and EEG normalization). However this case would be at the more severe end of the spectrum. Conclusion The status epilepticus during slow sleep can cause serious neurocognitive development alterations of children affected. Early age of onset and persistence of CSWS pattern significantly influence the prognosis of these patients. Our cases would confirm this assumption, because the delayed onset and benign course, despite one of them was a case of Landau–Kleffner syndrome. In a child with sudden decrease in school performance or language difficulties would be entirely necessary to carry out a study of sleep EEG. Acknowledgements Dres. Paloma Quintana, Julia Saez and Felix Paradinas.

Epilepsy surgery in children: Evaluation of seizure outcome and predictive elements

To analyze the clinical outcome of epilepsy surgery in children, and to identify the factors related with a favorable seizure control among several presurgical, surgical and postsurgical variables. One-hundred twenty children, younger than 16 years (69 male and 51 female), operated on for medically refractory focal epilepsy at the "C.Munari" Epilepsy Surgery Center of the Niguarda Hospital in Milan from 1998 to 2009, were identified. Seizure outcome was assessed according to the Engel's classification. Statistical analysis was performed to identify predictive elements of seizure outcome among several presurgical, surgical, and postsurgical variables. There were 84 (70%) seizure-free patients (Engel's classes Ia and Ic), 93 (77.5%) in class I, 8 (6.7%) in class II, 9 in class III (7.5%), and 10 (8.3%) in class IV. Our study confirms that epilepsy surgery is an established and effective treatment for partial epilepsy in children and suggest criteria to help identify early potential surgical candidates.

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.

Quantitative Analysis of Simultaneous EEG Features during PET Studies for Childhood Partial Epilepsy

PurposeTo demonstrate the significance of simultaneous electroencephalography (EEG) recording during 2-deoxy-2-[18F] fluoro-D-glucose (FDG)-positron emission tomography (PET) in childhood partial epilepsy.Materials and MethodsWe included 46 children with partial epilepsy who underwent simultaneous EEG during PET. We compared the epileptogenic area of several EEG features including epileptiform discharges, focal polymorphic slow waves, and electrographic seizures, with the abnormal metabolic region on PET. We also compared the epileptogenic area of simultaneous EEG and PET with findings on magnetic resonance imaging (MRI) and video/EEG, as well as the histopathological diagnosis of the resected cortical area, in eight patients who underwent surgical resection of the epileptogenic area.ResultsHypometabolic regions on interictal PET were concordant with epileptogenic areas of epileptiform discharges and focal polymorphic slow waves, according to their frequency and/or severity, with odds ratios of 1.35 and 1.81, respectively (p<0.05). Hypermetabolic PET was also concordant with epileptogenic areas of ictal events longer than 20 seconds during the period of FDG uptake. Among the eight patients who underwent surgical resection, six patients, including two with non-lesional MRI, had concordant EEG and PET findings, were confirmed pathologically, and became seizure-free after surgery.ConclusionSimultaneous EEG is useful in identifying epileptogenic areas due to a high concordance with abnormal PET metabolic areas. Moreover, simultaneous EEG may also prevent false lateralization of PET from postictal and mixed metabolism during ictal events, as well as abnormal hypermetabolism, during frequent interictal epileptiform discharges.

Effects of lamotrigine on cognition and behavior compared to carbamazepine as monotherapy for children with partial epilepsy

To compare the cognitive and behavioral effects of lamotrigine (LTG) to carbamazepine (CBZ) as monotherapy for pediatric epilepsy. A multicenter, randomized, open-label, parallel-group clinical trial was conducted in children with partial-onset seizures. LTG or CBZ was prescribed as monotherapy for previously untreated children and titrated over 8weeks, followed by maintenance for 24weeks. Outcome measures were change in cognition and behavior in a combined analysis of standardized measures from screening to the end of the maintenance phase, as well as antiepileptic efficacy and tolerability. A total of 67 children completed the study, including 32 of 43 (74.4%) treated with LTG and 35 of 41 (85.4%) treated with CBZ. Seizure-free outcomes did not differ between the intent-to-treat populations (53.5% LTG, 56.1% CBZ; p=0.81). There were no statistically significant differences in the intelligence of the two groups after treatment. Externalizing behavior problems improved in the CBZ group (p<0.05). However, there were no significant differences between the two groups in terms of externalizing behavior. The parents’ report on the Conner scale showed an improvement in the CBZ group compared to the LTG group (p<0.05). LTG and CBZ showed similar efficacy and cognitive effects in treating childhood partial epilepsy. However, CBZ showed more benefits in improving externalizing behaviors.