Benign Occipital Epilepsy Research Articles

Epileptic syndromes associated with focal clonic seizures

To study clinical, electroencephalographic and neuroimaging features in children with epileptic syndromes associated with focal clonic seizures (FCS). We examined 1258 patients with various forms of epilepsy with the onset of seizures from the first day of life to 18 years. FCS was identified in 263 patients (20.9%). FCS were included in the structure of 13 different epileptic syndromes: Rolandic epilepsy (28.1%), structural focal epilepsy (27.5%), structural focal epilepsy associated with benign epileptiform discharges of childhood (SFE-BEDC) (20.6%), focal epilepsy of unknown etiology (7.5%), epilepsia partialis continua (4.6%), pseudo-Lennox syndrome (3.4%), ESES syndrome (2.7%), Landau-Kleffner syndrome (1.5%), Dravet syndrome (1.1%), benign occipital epilepsy (1.1%), benign focal epilepsy in infancy (0.8%), MISF syndrome (0.8%), cognitive epileptiform disintegration (0.8%). In 50% of cases, epilepsy associated with FCS debuts before the age of 5 years (from 1 month to 18 years, average age 4.26±3.9). The groups of syndromes associated with FCS have different prognosis for remission of seizures. Prognostic predictors of seizure remission are: epileptic syndromes associated with BEDC, the presence of periventricular leukomalacia. A severe prognosis for the course of epilepsy is associated with local structural changes in the neocortex. Despite a favorable prognosis for seizures, continued diffuse interictal epileptiform activity with BEDC on the electroencephalogram is a predictor of the onset of cognitive impairment in children.

Heterozygous PGM3 Variants Are Associated With Idiopathic Focal Epilepsy With Incomplete Penetrance.

IntroductionIdiopathic focal epilepsy (IFE) is a group of self-limited epilepsies. The etiology for the majority of the patients with IFE remains elusive. We thus screened disease-causing variants in the patients with IFE.MethodsWhole-exome sequencing was performed in a cohort of 323 patients with IFE. Protein modeling was performed to predict the effects of missense variants. The genotype–phenotype correlation of the newly defined causative gene was analyzed.ResultsFour novel heterozygous variants in PGM3, including two de novo variants, were identified in four unrelated individuals with IFE. The variants included one truncating variant (c.1432C > T/p.Q478X) and three missense variants (c.478C > T/p.P160S, c.1239C > G/p.N413K, and c.1659T > A/p.N553K), which had no allele frequency in the gnomAD database. The missense variants were predicted to be damaging and affect hydrogen bonds with surrounding amino acids. Mutations Q478X, P160S, and N413K were associated with benign childhood epilepsy with centrotemporal electroencephalograph (EEG) spikes. P160S and N413K were located in the inner side of the enzyme active center. Mutation N553K was associated with benign occipital epilepsy with incomplete penetrance, located in the C-terminal of Domain 4. Further analysis demonstrated that previously reported biallelic PGM3 mutations were associated with severe immunodeficiency and/or congenital disorder of glycosylation, commonly accompanied by neurodevelopmental abnormalities, while monoallelic mutations were associated with milder symptoms like IFE.ConclusionThe genetic and molecular evidence from the present study implies that the PGM3 variants identified in IFE patients lead to defects of the PGM3 gene, suggesting that the PGM3 gene is potentially associated with epilepsy. The genotype–phenotype relationship of PGM3 mutations suggested a quantitative correlation between genetic impairment and phenotypic severity, which helps explain the mild symptoms and incomplete penetrance in individuals with IFE.

Exome sequencing in 57 patients with self-limited focal epilepsies of childhood with typical or atypical presentations suggests novel candidate genes.

Self-limited focal epilepsies of childhood (SFEC) are amongst the best defined and most frequent epilepsy syndromes affecting children with usually normal developmental milestones. They include core syndromes such as Rolandic epilepsy or "Benign" epilepsy with Centro-Temporal Spikes and the benign occipital epilepsies, the early onset Panayiotopoulos syndrome and the late-onset Gastaut type. Atypical forms exist for all of them. Atypical Rolandic epilepsies are conceptualized as belonging to a continuum reaching from the "benign" RE to the severe end of the Landau-Kleffner (LKS) and Continuous Spike-Waves during Sleep syndromes (CSWS). GRIN2A has been shown to cause the epilepsy-aphasia continuum that includes some patients with atypical Rolandic epilepsy with frequent speech disorders, LKS and CSWS. In the present study, we searched novel genes causing SFEC with typical or atypical presentations. Exome sequencing was performed in 57 trios. Patients presented with typical or atypical SFEC, negative for GRIN2A pathogenic variant. We found rare candidate variants in 20 patients. Thirteen had occurred de novo and were mostly associated to atypical Rolandic Epilepsy. Two of them could be considered as disease related: a null variant in GRIN2B and a missense variant in CAMK2A. Others were considered good candidates, including a substitution affecting a splice site in CACNG2 and missense variants in genes encoding enzymes involved in chromatin remodeling. Our results further illustrate the fact that atypical SFEC are more likely to have Mendelian inheritance than typical SFEC.

The Spectrum of Epilepsies with Fixation off Sensitivity: A Case Report and Review of Literature

Fixation off sensistivity is a electrographic marker of occipital lobe epilepsy. The report describes a 11 year old with infrequent seizures responsive to treatment with valproate who was found to have occipital epileptiform discharges which appeared only during eye closure. The typical phenomenology of visual aura or autonomic seizures as seen in benign occipital epilepsies is not mandatory to be associated with FOS. The spectrum of various epilepsy syndrome which display this typical finding is discussed.

Early Onset Benign Occipital Epilepsy (Panayiotopoulos syndrome): a case Report & Literature Review

Panayiotopoulos syndrome is a type of benign childhood epilepsy syndrome characterized by episodic autonomic and mainly emetic symptoms. It predominantly affects children of 3-6 years of age (13% of those with one or more non-febrile seizures). EEG shows great variability, with occipital, extra-occipital spikes or brief generalised discharges alone or in combination; it may also be consistently normal. Despite the high prevalence of autonomic status epilepticus, the prognosis of Panayiotopoulos syndrome is usually excellent and most do not require anti epileptic medications. Remission usually occurs within 1-2 years from onset. One third have a single seizure but 5-10% may have more than 10 seizures or a more prolonged course. We present a 5 year old boy with this condition, who presented with episodes of severe vomiting, deviation of eyes, focal seizure, altered sensorium, characteristic EEG in the form of multiple occipital spikes and normal neuroimaging studies.J. Natl Inst. Neurosci Bangladesh 2015;1(1):27-30

First-drug treatment failures in 42 Turkish children with idiopathic childhood occipital epilepsies.

Background:The early and late benign occipital epilepsies of childhood (BOEC) are described as two discrete electro-clinical syndromes, eponymously known as Panayiotopoulos and Gastaut syndromes. The purpose of this study was to identify predictors of failure to respond to the initial antiepileptic drug (AED).Materials and Methods:A total of 42 children with BOEC were enrolled. Predictive factors were analyzed by survival methods.Results:Among the 42, 25 patients (59.5%) were boys and 17 (40.5%) were girls and the mean age at the seizure onset was 7.46 ± 2.65 years (4–14 years). Of the 42 patients, 34 (81.0%) were treated relatively successfully with the first AED treatment, and 8 (19.0%) were not responded initial AED treatment. There was no correlation between response to initial AED treatment and sex, consanguinity, epilepsy history of family, age of seizure onset, frequency of seizures, history of status epilepticus, duration of starting first treatment, findings on electroencephalogram. However, history of febrile seizure and type of BOEC were significantly associated with failure risk.Conclusions:Factors predicting failure to respond to the AED were history of febrile seizure and type of BOEC in children with BOEC.

Benign occipital epilepsy of childhood: panayiotopoulos syndrome in a 3 year old child

Panayiotopoulos syndrome (PS) is a relatively frequent and benign epileptic syndrome seen in children in the age group of 3-6 years and is characterised by predominantly autonomic symptoms and/or simple motor focal seizures followed or not by impairment of consciousness. Although multifocal spikes with high amplitude sharp-slow wave complexes at various locations can be present in the EEG, interictal electroencephalogram (EEG) in children with this particular type of epilepsy characteristically shows occipital spikes. This syndrome has known to be a masquerader and can imitate gastroenteritis, encephalitis, syncope, migraine, sleep disorders or metabolic diseases. In the absence of thorough knowledge of types of benign epilepsy syndromes and their various clinical presentations, epilepsy such as PS can be easily missed. The peculiar aspects of this type of epilepsy in children should be known not only by paediatricians but also by general doctors because a correct diagnosis would avoid aggressive interventions and concerns on account of its benign outcome. In this case study, we report a case of PS in a 3 year old child.

Divergent effects of the T1174S SCN1A mutation associated with seizures and hemiplegic migraine

To report the identification of the T1174S SCN1A (NaV 1.1) mutation in a three-generation family with both epileptic and familial hemiplegic migraine (FHM) phenotypes and clarify the pathomechanism. The five affected individuals underwent detailed clinical analyses. Mutation analyses was performed by direct sequencing of SCN1A; functional studies by expression in tsA-201 cells. A computational model was used to compare the effects of T1174S with those of a typical FHM mutation (Q1489K). The proband had benign occipital epilepsy (BOE); two relatives had simple febrile seizures (FS) and later developed BOE. Two additional relatives had FHM without epilepsy or FS. All affected members and one obliged carrier carried the T1174S mutation. Functional effects were divergent: positive shift of the activation curve and deceleration of recovery from fast inactivation, consistent with loss of function, and increase of persistent current (I(NaP)), consistent with gain of function. The I(NaP) increase was inhibited by dialysis of the cytoplasm, consistent with a modulation. Therefore, as shown by the computational model, T1174S could in some conditions induce overall loss of function, and in others gain of function; Q1489K induced gain of function in all the conditions. Modulation of the properties of T1174S can lead to a switch between overall gain and loss of function, consistent with a switch between promigraine end epileptogenic effect and, thus, with coexistence of epileptic and FHM phenotypes in the same family. These findings may help to shed light on the complex genotype-phenotype relationship of SCN1A mutations.

Siblings with refractory occipital epilepsy showing localized network activity on EEG‐fMRI

The benign occipital epilepsies of childhood include Panayiotopoulos and Gastaut syndromes; a third syndrome, idiopathic photosensitive occipital epilepsy may also begin in childhood or adolescence. We describe siblings with occipital epilepsy characterized by refractory, frequent, brief visual seizures and normal magnetic resonance imaging (MRI). Electroencephalography (EEG) with functional MRI (fMRI) supports localization of interictal epileptiform activity to the occipital lobes. Our hypothesis is that the siblings share a genetic focal epilepsy arising from a localized occipital network. Although they share many features of Gastaut syndrome, their refractory ongoing seizures in adolescence is unusual and likely due to underlying genetic determinants.

Childhood epileptic seizures imitating migraine and encephalitis

Paroxismal events can resemble epileptic seizures, however, some epileptic seizures, especially benign occipital childhood epilepsies can imitate migraine, cycling vomiting or encephalitis. The aim of this study was evaluation of clinical and electroencephalographic (EEG) features and outcome in children with benign occipital childhood epilepsies. Investigation included 18 patients with benign occipital childhood epilepsies hospitalized in the period from 2007 to 2010. The diagnosis was based on clinical and EEG characteristics of seizures, while treatment included acute therapy for seizures and chronic antiepileptic drugs. Prognosis was analyzed in terms of neurological outcome and seizure recurrence rate. Benign occipital childhood epilepsy with early onset was diagnosed in 15 children. Vegetative symptoms, mostly ictal vomiting (13), eye deviation and loss of consciousness (13) dominated in the clinical presentation. The most frequent EEG findings showed occipital epileptic discharges. Benign occipital childhood epilepsy with late onset was diagnosed in three cases. Seizures were manifested by visual hallucinations, headache and secondary generalized convulsions. All three patients were administered chronic antiepileptic drugs and had good outcome. In our patients, clinical manifestations of benign occipital epilepsies had some similarities with clinical features of migraine and encephalitis. It could explain misdiagnosis in some of them. Knowledge about main features and differences between each of these disorders is crucial for making appropriate diagnosis.

Clinical and electroencephalographic characteristics of benign occipital epilepsy of childhood in two tertiary Brazilian hospitals

This study intended to investigate the clinical and electroencephalographic benign occipital epilepsy of childhood (BOEC) characteristics in a population sample of patients from two tertiary Brazilian hospitals. We analyzed retrospectively 4912 electroencephalograms (EEGs) records, and the included patients were submitted to a new clinical and EEG evaluation. Were included 12 (0.92%) patients; 4 (33.3%) with criteria for early BOEC; 6 (50%) for late form and 2 (16.7%) with superimposed early and late onset forms. After new investigation, 2 (16.7%) had normal EEG; 4 (33.3%) had paroxysms over the occipital region; 3 (25%) over the temporal posterior regions and 3 (25%) over the posterior regions. Sharp waves were the predominant change, occurring in 8 (66.6%); spike and slow wave complexes in 1 (8.3%) and sharp and slow wave complexes in 1 (8.3%). Vomiting, headache and visual hallucinations were the most common ictal manifestations, presented in 100% of patients with superimposed forms. Vomiting were absent in the late form and headache was present in all forms of BOEC.

Benign partial seizures of adolescence

Benign partial seizures of adolescence (BPSA) presents as partial seizures with or without secondary generalization occurring isolated or in a cluster in the first 24 to 48 hours after onset in adolescents. Correct recognition of this entity can avoid use of antiepileptic drugs and associated risks. We conducted retrospective review of charts to identify seven cases of BPSA between 11-15 years at presentation who did not have generalized epilepsy, benign rolandic epilepsy, benign occipital epilepsy, an epileptogenic lesion on neuroimaging, or unprovoked recurrent tonic-clonic seizures. All of them had partial seizures, normal neuroimaging and electroencephalogram with no recurrence of seizures despite no treatment.

Late-onset childhood occipital epilepsy. An unusual case in adolescence and differential diagnosis with migraine

INTRODUCTION: The new proposed classification of ILAE Task Force (2001) proposes that the occipital epilepsies should be split into two subtypes: an early-onset benign childhood occipital epilepsy (or Panayiotopoulos type) and late-onset childhood occipital epilepsy (or Gastaut type). Migraine with visual aura must be considered as a differential diagnosis in childhood and adolescents with occipital epilepsy without motor phenomena. OBJECTIVE: The goal of our paper is to report the case a 16-year-old female, with normal psychomotor development, that during the lunch time presented an event characterized by the vision of multiple colored spots which were moving horizontally and vertically and also in circles through the visual field. Minutes after the visual event, the patient referred to a severe diffuse throbbing headache with frontal predominance. During the clinical investigation was submitted to a video-electroencephalogram exam for 12 hours with, reveling occipital sharp-waves discharges in occipital right region as well as in occipital left region. CONCLUSION: We reported of such classic type of epileptic syndrome in a patient in the unusual age of onset, the end of adolescence, considering the differential diagnosis with migraine with visual aura.

Benign occipital epilepsies of childhood: clinical features and genetics

The early and late benign occipital epilepsies of childhood (BOEC) are described as two discrete electro-clinical syndromes, eponymously known as Panayiotopoulos and Gastaut syndromes. Our aim was to explore the clinical features, classification and clinical genetics of these syndromes using twin and multiplex family studies to determine whether they are indeed distinct. Sixteen probands including seven twins were studied. Non-twin probands (n = 9) with a family history of epilepsy were included. Electroclinical seizure semiology was characterized and probands were classified into BOEC syndromes. Detailed phenotyping of relatives was performed and phenotypic patterns within families were analysed. One-third of the children in this selected series of BOEC did not have a pure syndrome, rather a mixed syndrome with features of both Panayiotopoulos and Gastaut syndromes. Monozygotic twin pairs did not show a higher concordance rate than dizygotic twin pairs suggesting that BOEC may not be a purely genetic disorder. In relatives with epilepsy, there was a mixed pattern of focal and generalized epilepsies with focal epilepsies predominating. BOEC is an electro-clinical spectrum with Panayiotopoulos and Gastaut syndromes at either end; many cases show mixed features. Clinical genetic studies highlight the multifactorial aetiology of BOEC as monozygotic twins have low concordance suggesting that non-conventional genetic influences or environmental factors play a major role. Family studies show both focal and generalized epilepsies reinforcing that these are not discrete categories of idiopathic epilepsies and are likely to share genetic determinants.

Inverted Fixation-Off Sensitivity in Atypical Benign Partial Epilepsy

Fixation-off sensitivity is an electroencephalographic phenomenon characterized by spike-and-wave discharges that only occur when central vision and fixation are eliminated. It is especially seen in children with Panayiotopoulos-type, early-onset, benign childhood occipital epilepsy or Gastaut type, late-onset, childhood occipital epilepsy. It can also be seen in eyelid myoclonia with absences, in other idiopathic generalized epilepsies, and in asymptomatic children without epilepsy. We describe a boy with atypical, benign partial epilepsy of childhood who exhibited the reverse: epileptiform activity that was suppressed by the absence of central vision or fixation, and activated by central vision or fixation.

What’s new in: “Genetics in childhood epilepsy”

In recent years, different mutations in genes that control the excitability of neurons have been described in idiopathic childhood epilepsies. Most commonly, sodium/potassium channelopathies and GABA-receptor mutations are involved. Major progress has been made in the field of idiopathic generalised epilepsies associated with febrile seizures (GEFS+). It now is becoming clear that mutations should not only be looked for in familial cases, but also in sporadic cases, especially in infants and young children with unexplained severe epileptic encephalopathies. Many studies also define 'epilepsy susceptibility genes', which contribute to one's individual genetic vulnerability to develop epilepsy. It should be realized, however, that in the most common idiopathic benign childhood epilepsies (benign rolandic and occipital epilepsies), major breakthroughs are still awaited. In addition, a better clinical description of the epileptic phenotypes is needed to explain more precisely the genotypic and phenotypic heterogeneity. Genetic studies are nowadays becoming a necessary diagnostic step in the evaluation of idiopathic childhood epilepsies, not only in familial cases, but also in sporadic cases.

The new ILAE Report on Classification and Evidence‐Based Commentary on Panayiotopoulos Syndrome and Autonomic Status Epilepticus

The new ILAE Report on Classification and Evidence‐Based Commentary on Panayiotopoulos Syndrome and Autonomic Status Epilepticus

Atypical Clinical Picture in a Patient with Benign Occipital Epilepsy: Diagnostic Contribution of Morpho-Functional MR

Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a maternally inherited disease due to mitochondrial DNA (mtDNA) point mutations. The clinical phenotype varies in relation to the systems affected, age at onset and disease severity. The characteristic signs of MELAS are nausea and vomiting due to acidosis, headache, epilepsy, ataxia or generalized weakness, ophthalmoplegia, motor and sensory focal neurological deficits. The clinical course may improve due to partial regression of the typical lesions, but the prognosis is usually adverse. A 19-year-old man with a diagnosis of benign occipital epilepsy and resumption of seizure activity with focal occipital attacks since the age of 14 years came to our attention for the recent onset of drug-resistant electroclinical seizures of long duration with complex symptoms, where the dominant clinical feature was an intense, persistent bilateral periorbital migraine with nausea and vomiting, scintillation scotomata and blurring of vision. MR studies were performed at our institution in the immediate post-seizure phase and then at one week, three and six months. The acute-phase morphological scans showed a right cortical-subcortical area with altered signal in the occipitopolar region that was hypointense on T1 and hyperintense on T2 and FLAIR, with cortical thickening and effacement of the sulci. Contrast-enhanced scans did not demonstrate BBB alterations. The DWI scans showed a right temporo-occipital cortical area with higher signal intensity. In the subsequent examinations the area with altered signal shrank gradually and significantly in parallel with improvement in clinical conditions. The diagnostic hypothesis of benign occipital epilepsy was consistent neither with the clinical course, characterized by persistent headache, visual disturbance and refractoriness to antiepileptic drugs, nor with the temporal-occipital cortical MR findings, which resembled ischemic lesions but displayed a non-territorial pattern as well as reversibility over time. These elements guided in the diagnosis of MELAS, which was subsequently confirmed by identification of the typical gene mutation. On DWI the stroke-like lesions of MELAS are seen more frequently as focal hyperintense areas compared with healthy parenchyma. Such high signal intensity likely corresponds to T2 shine-through rather than cytotoxic edema. Indeed, several studies have demonstrated that in acute-phase scans of MELAS stroke-like lesions DWI hyperintensity is associated with increased ADC values that are not associated with restricted water diffusivity, reflecting the metabolic rather than anoxic-ischemic nature of these changes. In the present case, morphological MR associated with DWI was very helpful in guiding the diagnosis by demonstrating some pathognomonic features of MELAS stroke-like lesions such as cortical-subcortical involvement of the posterior hemispheres, the non-territorial pattern, lesion reversibility and the pathophysiological role of vasogenic edema in inducing an increase in extracellular water and thus in diffusion values.

Estudio epidemiológico, clínico y evolutivo de 37 pacientes con epilepsia occipital benigna infantil de comienzo precoz

To analyse the epidemiological, clinical and developmental characteristics of early-onset benign occipital epilepsy of childhood in order to facilitate its diagnostic suspicion in daily clinical practice. The medical records of 37 patients with early-onset benign occipital epilepsy of childhood were reviewed in order to collect epidemiological and clinical features, results of complementary examinations and developmental data. The diagnostic criteria applied were those of the ILAE (International League Against Epilepsy). The mean age at diagnosis was 5.4 years. In all, 64.9% were diagnosed at a pre-school age, with a greater prevalence of females (67.6%). The mean number of seizures per patient was 3.3 and they were mainly characterised by impaired consciousness (90.3%), vomiting (70.1%), eye deviation and/or headaches (30.6%), and generalised (32.8%) or partial (11.2%) motor crises. Seizures occurred during sleep in 67.2% of cases. In 28 cases (75.7%) occipital paroxysms were observed that coexisted with generalised and/or multifocal paroxysms. Of all recurrences, 71.3% occurred during the first 6 months, and from 2 years onwards 82.9% of the patients had no seizures; no developmental differences were found between treated and non-treated patients. One patient with an atypical development was recorded. Early-onset benign occipital epilepsy of childhood is relatively frequent at the paediatric age, especially in the pre-school years. Although its semiological sequence is quite characteristic, the fact that it lacks clinical and neurological specificity makes diagnostic suspicion more difficult. Its prognosis is especially favourable; however, since their progress may develop in an atypical manner, a rigorous developmental control of these patients would be of the highest priority.

The Spectrum of Idiopathic Rolandic Epilepsy Syndromes and Idiopathic Occipital Epilepsies: From the Benign to the Disabling

Benign childhood epilepsy with centrotemporal spikes (BCECTS) is an idiopathic focal epilepsy syndrome, the benign characteristics of which are debated; in fact, stable or intermittent specific neuropsychological deficits are frequent and may affect scholastic or adaptive abilities. Cognitive dysfunction may be related to a marked increment of the interictal epileptic discharges in NREM sleep: different degrees of neuropsychological deficits depend on the extent of awake and sleep activity and the predominant discharge localization. The age of onset and duration of atypical sleep EEG patterns may correlate with permanent cognitive impairments. These atypical clinical and EEG evolutions have been reported in the literature as different syndromes that constitute the spectrum of idiopathic rolandic epilepsy. Moreover, a clinical link between BCECTS and early-onset benign childhood occipital epilepsy has been demonstrated. According to the neurobiological approach, the spectrum of Idiopathic Rolandic Epilepsy is based on an age-dependent, idiopathic predisposition to focal seizures and sharp-wave discharges, as an expression of nonlesional cortical excitability. The involvement of a given area of the cerebral cortex may depend on the brain maturational stage.