Self-limited Focal Epilepsy Research Articles

Minor Neurological Dysfunction: A Comparative Study in Pediatrics with Different Types of Focal Epilepsy

AbstractEpilepsy is a disorder that occurs as a result of abnormal neuronal discharges in the brain and affects approximately 1% of children. Sensorimotor function impairments that are related to minor neurological deficits may be seen even in children diagnosed with epilepsy solely. This study aims to determine the type and areas of minor neurological dysfunction (MND) in children with Self-Limited Focal Epilepsy (SeLFE) and to compare the children with Self-Limited Epilepsy with Centrotemporal Spikes (SeLECTS) and SeLFE without SeLECTS. Fifty-six children diagnosed with epilepsy (28 SeLECTS and 28 SeLFE without SeLECTS) were included in the study. Both groups consisted of 13 girls and 15 boys. The mean ages of SeLECTS and SeLFE without SeLECTS groups were 9.68 ± 1.63 and 9.32 ± 1.62, respectively. A Modified Touwen Neurological Examination was performed to determine the type and areas of MND. There were no differences between the groups regarding MND type, coordination, fine manipulation, sensory, and involuntary movement areas (p > 0.05). It should be considered that children with SeLECTS may be neurologically affected as much as children with other types of epilepsy. Long-term problems due to epilepsy may be minimized by short-term neurodevelopmental follow-ups.

Maturation-dependent changes in cortical and thalamic activity during sleep slow waves: Insights from a combined EEG-fMRI study

IntroductionStudies using scalp EEG have shown that slow waves (0.5–4 Hz), the most prominent hallmark of NREM sleep, undergo relevant changes from childhood to adulthood, mirroring brain structural modifications and the acquisition of cognitive skills. Here we used simultaneous EEG-fMRI to investigate the cortical and subcortical correlates of slow waves in school-age children and determine their relative developmental changes. MethodsWe analyzed data from 14 school-age children with self-limited focal epilepsy of childhood who fell asleep during EEG-fMRI recordings. Brain regions associated with slow-wave occurrence were identified using a voxel-wise regression that also modelled interictal epileptic discharges and sleep spindles. At the group level, a mixed-effects linear model was used. The results were qualitatively compared with those obtained from 2 adolescents with epilepsy and 17 healthy adults. ResultsSlow waves were associated with hemodynamic-signal decreases in bilateral somatomotor areas. Such changes extended more posteriorly relative to those in adults. Moreover, the involvement of areas belonging to the default mode network changes as a function of age. No significant hemodynamic responses were observed in subcortical structures. However, we identified a significant correlation between age and thalamic hemodynamic changes. ConclusionsPresent findings indicate that the somatomotor cortex may have a key role in slow-wave expression throughout the lifespan. At the same time, they are consistent with a posterior-to-anterior shift in slow-wave distribution mirroring brain maturational changes. Finally, our results suggest that slow-wave changes may not reflect only neocortical modifications but also the maturation of subcortical structures, including the thalamus.

How the Spreading and Intensity of Interictal Epileptic Activity Are Associated with Visuo-Spatial Skills in Children with Self-Limited Focal Epilepsy with Centro-Temporal Spikes.

This paper investigates brain-behaviour associations between interictal epileptic discharges and cognitive performance in a population of children with self-limited focal epilepsy with centro-temporal spikes (SeLECTS). Sixteen patients with SeLECTS underwent an extensive neuropsychological assessment, including verbal short-term and episodic memory, non-verbal short-term memory, attentional abilities and executive function. Two quantitative EEG indices were analysed, i.e., the Spike Wave Index (SWI) and the Spike Wave Frequency (SWF), and one qualitative EEG index, i.e., the EEG score, was used to evaluate the spreading of focal SW to other parts of the brain. We investigated associations between EEG indices and neuropsychological performance with non-parametric Spearman correlation analyses, including correction for multiple comparisons. The results showed a significant negative correlation between (i) the awake EEG score and the Block Tapping Test, a visuo-spatial short-term memory task, and (ii) the sleep SWI and the Tower of London, a visuo-spatial planning task (pcorr < 0.05). These findings suggest that, in addition to the usual quantitative EEG indices, the EEG analysis should include the qualitative EEG score evaluating the spreading of focal SW to other parts of the brain and that neuropsychological assessment should include visuo-spatial skills.

CLINICAL FEATURES, ELECTROENCEPHALOGRAM FINDINGS AND TREATMENT OF SELF-LIMITED FOCAL EPILEPSIES OF CHILDHOOD

Objectives: The objective is to study the clinical features of self-limited focal epilepsies of childhood and to describe their electroencephalogram (EEG) findings and treatment. Methods: Twenty cases of self-limited focal epilepsies of childhood attending the Department of Neurology Government Medical College, Kozhikode, between August 2019 and July 2020 were included in the study. Details of history, examination, EEG, and treatment were collected. Results: The age at first seizure was 1.5–12 years. Most children were diagnosed with self-limited focal epilepsy of childhood with centrotemporal spikes. One child had Panayiotopoulos syndrome. Most of the seizures occurred during sleep. The majority were generalized tonic–clonic seizures. The majority had bilateral centrotemporal spikes in EEG. The child with Panayiotopoulos had bilateral spikes from the posterior head region. All were treated with antiepileptics. Conclusion: Self-limited focal epilepsy of childhood with centrotemporal spikes was the most common self-limited focal epilepsy of childhood. They had typical centrotemporal epileptiform discharges, seen bilaterally in most. The most commonly used drug was valproate. None had any major adverse effects on therapy.

Epileptic nystagmus as clinical manifestation of self-limited focal epilepsy: Rethinking etiology and prognostic value and literature review.

Epileptic nystagmus (EN) is an uncommon ictal clinical manifestation characterized by rapid, repetitive eyeballs movements. Few cases of EN have been reported and, in most cases, electro-clinical correlation showed a focal EEG activity, mainly in the occipital and temporo-occipital areas. Although EN occurs both in idiopathic and non-idiopathic epilepsy, the most frequent cause appears to be inborn or acquired alteration of brain structures. We report of a 12-year-old girl with EN as ictal manifestation of self-limited focal seizures. We described clinical manifestations, electroencephalographic features, treatment, and follow-up, presenting the ictal video-EEG phenomenon. Alongside, we reviewed the reported clinical features of the few pediatric cases (seven patients) with idiopathic epileptic nystagmus through a systematic literature review. Isolated Epileptic Nystagmus (IEN) is much rarer than EN, as it is more frequently associated with other types of seizures, and can be idiopathic, especially in children. Epilepsy prognosis is usually favorable with appropriate treatment, and ASM discontinuation seems to be successful after few years of treatment.

Self-limited childhood epilepsies are disorders of the perisylvian communication system, carrying the risk of progress to epileptic encephalopathies-Critical review.

"Sleep plasticity is a double-edged sword: a powerful machinery of neural build-up, with a risk to epileptic derailment." We aimed to review the types of self-limited focal epilepsies..."i.e. keep as two separate paragraphs" We aimed to review the types of self-limited focal epilepsies: (1) self-limited focal childhood epilepsy with centrotemporal spikes, (2) atypical Rolandic epilepsy, and (3) electrical status epilepticus in sleep with mental consequences, including Landau-Kleffner-type acquired aphasia, showing their spectral relationship and discussing the debated topics. Our endeavor is to support the system epilepsy concept in this group of epilepsies, using them as models for epileptogenesis in general. The spectral continuity of the involved conditions is evidenced by several features: language impairment, the overarching presence of centrotemporal spikes and ripples (with changing electromorphology across the spectrum), the essential timely and spatial independence of interictal epileptic discharges from seizures, NREM sleep relatedness, and the existence of the intermediate-severity "atypical" forms. These epilepsies might be the consequences of a genetically determined transitory developmental failure, reflected by widespread neuropsychological symptoms originating from the perisylvian network that have distinct time and space relations from secondary epilepsy itself. The involved epilepsies carry the risk of progression to severe, potentially irreversible encephalopathic forms.

Serum Levels of Neuropeptides in Epileptic Encephalopathy With Spike-and-Wave Activation in Sleep

BackgroundEpileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS) is a syndrome of childhood, characterized by diffuse or generalized spike-wave activity in electroencephalography during non–rapid eye movement sleep. Neuropeptides have been demonstrated in several studies to function in the sleep-wake cycle and display convulsant and anticonvulsant features. In this study, we aimed to investigate the relationship between EE-SWAS and neuropeptides such as dynorphin, galanin, ghrelin, leptin, melatonin, and orexin. MethodsThis multicenter study was conducted from July 2019 to January 2021. There were three groups: Group 1 contained patients with EE-SWAS. Group 2 consisted of patients with self-limited focal epilepsy of childhood (SeLFE), and group 3 was the control group. Levels of neuropeptides were compared in the sera of these three groups. ResultsThere were 59 children aged between four and 15 years. Group 1 contained 14 children, group 2 contained 24 children, and group 3 contained 21 children. The level of leptin is higher and the level of melatonin is lower in group 1 than in group 3 (P = 0.01 and P = 0.005, respectively). In group 3, the level of orexin was lower than in both groups 2 and 3 (P = 0.01 and P = 0.01). ConclusionsThese data show that the level of leptin was higher and the level of melatonin was lower in patients with EE-SWAS than in the control group. Furthermore, patients with EE-SWAS had lower orexin levels than both the control group and patients with SeLFE. Further research is required to understand the potential role of these neuropeptides in the pathophysiology of EE-SWAS.

Etiology and duration of the disease in the assessment of intellectual functioning of pediatric patients with epilepsy: An observational study

Childhood epilepsy can be frequently associated with impaired cognitive functioning. Previous research has suggested an increased risk of cognitive impairment that may be related to the etiology, the electro-clinical pattern and the load of anti-seizure medications (ASMs). The aim of this study was to evaluate the impact of different clinical features on the global intellectual functioning in a cohort of children and adolescents with epilepsy. We studied eighty patients diagnosed and followed in a tertiary care center. These factors were examined: 1. Etiology of epileptic syndrome; 2. Type of seizure; 3. Number of ASMs; 4. Seizure frequency; 5. Age at seizure onset; 6. Total duration of epilepsy; and 7. Active duration of epilepsy. Multiple regression analysis showed that the etiology and the total duration of epilepsy were the best indicators of intellectual functioning. The present data indicate that children with symptomatic epilepsy (SE) have lower IQ scores (M = 63.5), while children with self-limited focal epilepsy and generalized idiopathic epilepsy, i.e. age-related epileptic syndromes (ARES), have a higher IQ (M = 100.0; p < 0.01). Children with epilepsy of unknown etiology (UEE) (M = 75.1; p < 0.05) are positioned at an intermediate level between the SE and the ARES group (p < 0.01). Increased duration of epilepsy was associated with decreased intellectual functioning. In conclusion, knowledge about the risks associated with etiologic factors and the duration of the disease may guide the definition of optimal neuropsychological rehabilitation strategies.

Focal epilepsies: update on diagnosis and classification.

Correctly diagnosing and classifying seizures and epilepsies is paramount to ensure the delivery of optimal care to patients with epilepsy. Focal seizures, defined as those that originate within networks limited to one hemisphere, are primarily subdivided into focal aware, focal impaired awareness, and focal to bilateral tonic-clonic seizures. Focal epilepsies account for most epilepsy cases both in children and adults. In children, focal epilepsies are typically subdivided in three groups: self-limited focal epilepsy syndromes (e.g., self-limited epilepsy with centrotemporal spikes), focal epilepsy of unknown cause but which do not meet criteria for a self-limited focal epilepsy syndrome, and focal epilepsy of known cause (e.g., structural lesions - developmental or acquired). In adults, focal epilepsies are often acquired and may be caused by a structural lesion such as stroke, infection and traumatic brain injury, or brain tumors, vascular malformations, metabolic disorders, autoimmune, and/or genetic causes. In addition to seizure semiology, neuroimaging, neurophysiology, and neuropathology constitute the cornerstones of a diagnostic evaluation. Patients with focal epilepsy who become drug-resistant should promptly undergo assessment in an epilepsy center. After excluding pseudo-resistance, these patients should be considered for presurgical evaluation as a means to identify the location and extent of the epileptogenic zone and assess their candidacy for a surgical procedure. The goal of this seminar in epileptology is to summarize clinically relevant information concerning focal epilepsies. This contributes to the ILAE's mission to ensure that worldwide healthcare professionals, patients, and caregivers continue to have access to high-quality educational resources concerning epilepsy.

Neurocognitive and psychological comorbidities in patients with self-limited centrotemporal spike epilepsy. A case-control study.

Self-limited epilepsy with centrotemporal spikes (SeLECTS) is the most frequent self-limited focal epilepsy. This study aimed to assess the cognitive, behavioral, and other neuropsychological aspects of children with SeLECTS, and compare them with a control group. A case-control study was carried out between January and May 2022. Patients with SeLECTS, aged between 6 and 18 years, and followed-up at our hospital were selected for inclusion in the study. For each case, two age-matched controls were opportunistically recruited. All the participants performed the EpiTrack Junior® test, and their parents filled out the Child Behavior Checklist (CBCL). Eighteen patients were included (mean age: 8.7 ± 1.7 years). At SeLECTS' diagnosis, 83% of cases had adequate psychomotor development, and 17% had a neurodevelopmental disorder. The EpiTrack-Junior® and the Total Problems CBCL scores were not influenced by the laterality of the epileptic focus nor by the number of seizures. 61% of cases showed mild or significant impairment in the EpiTrack-Junior® test versus 44% of controls (p = 0.712), and 39% of cases vs. 14% of controls had 'clinically significant' scores on the Total Problems CBCL scale (p = 0.087). Although this study did not find statistically significant differences between cases and controls, it should be noted that most patients with SeLECTS had a mild or significant disability in executive functions. A considerable percentage of cases were in the pathological range regarding emotional/behavioral problems. This study highlights the importance of screening the cognitive, behavioral, and emotional problems in all patients with SeLECTS.

Epilepsy syndromes in cerebral palsy: varied, evolving and mostly self-limited.

Seizures occur in approximately one-third of children with cerebral palsy. This study aimed to determine epilepsy syndromes in children with seizures and cerebral palsy due to vascular injury, anticipating that this would inform treatment and prognosis. We studied a population-based cohort of children with cerebral palsy due to prenatal or perinatal vascular injuries, born 1999-2006. Each child's MRI was reviewed to characterize patterns of grey and white matter injury. Children with syndromic or likely genetic causes of cerebral palsy were excluded, given their inherent association with epilepsy and our aim to study a homogeneous cohort of classical cerebral palsy. Chart review, parent interview and EEGs were used to determine epilepsy syndromes and seizure outcomes. Of 256 children, 93 (36%) had one or more febrile or afebrile seizures beyond the neonatal period and 87 (34%) had epilepsy. Children with seizures were more likely to have had neonatal seizures, have spastic quadriplegic cerebral palsy and function within Gross Motor Function Classification System level IV or V. Fifty-six (60%) children with seizures had electroclinical features of a self-limited focal epilepsy of childhood; we diagnosed these children with a self-limited focal epilepsy-variant given the current International League Against Epilepsy classification precludes a diagnosis of self-limited focal epilepsy in children with a brain lesion. Other epilepsy syndromes were focal epilepsy-not otherwise specified in 28, infantile spasms syndrome in 11, Lennox-Gastaut syndrome in three, genetic generalized epilepsies in two and febrile seizures in nine. No epilepsy syndrome could be assigned in seven children with no EEG. Twenty-one changed syndrome classification during childhood. Self-limited focal epilepsy-variant usually manifested with a mix of autonomic and brachio-facial motor features, and occipital and/or centro-temporal spikes on EEG. Of those with self-limited focal epilepsy-variant, 42/56 (75%) had not had a seizure for >2 years. Favourable seizure outcomes were also seen in some children with infantile spasms syndrome and focal epilepsy-not otherwise specified. Of the 93 children with seizures, at last follow-up (mean age 15 years), 61/91 (67%) had not had a seizure in >2 years. Children with cerebral palsy and seizures can be assigned specific epilepsy syndrome diagnoses typically reserved for normally developing children, those syndromes commonly being age-dependent and self-limited. Compared to typically developing children with epilepsy, self-limited focal epilepsy-variant occurs much more commonly in children with cerebral palsy and epilepsy. These findings have important implications for treatment and prognosis of epilepsy in cerebral palsy, and research into pathogenesis of self-limited focal epilepsy.

Genetic Epilepsy Syndromes.

This article reviews the clinical features, typical EEG findings, treatment, prognosis, and underlying molecular etiologies of the more common genetic epilepsy syndromes. Genetic generalized epilepsy, self-limited focal epilepsy of childhood, self-limited neonatal and infantile epilepsy, select developmental and epileptic encephalopathies, progressive myoclonus epilepsies, sleep-related hypermotor epilepsy, photosensitive occipital lobe epilepsy, and focal epilepsy with auditory features are discussed. Also reviewed are two familial epilepsy syndromes: genetic epilepsy with febrile seizures plus and familial focal epilepsy with variable foci. Recent years have seen considerable advances in our understanding of the genetic factors underlying genetic epilepsy syndromes. New therapies are emerging for some of these conditions; in some cases, these precision medicine approaches may dramatically improve the prognosis. Many recognizable genetic epilepsy syndromes exist, the identification of which is a crucial skill for neurologists, particularly those who work with children. Proper diagnosis of the electroclinical syndrome allows for appropriate treatment choices and counseling regarding prognosis and possible comorbidities.

Self-limited focal epilepsy in a young child with SARS-CoV-2.

Self-limited focal epilepsy in a young child with SARS-CoV-2.

Self-limited epilepsy of childhood with affective seizures: A well-defined epileptic syndrome?

ObjectiveHere we present cases of focal epilepsy with affective symptoms analyzing seizure characteristics, EEG pattern, treatment, and outcome. MethodsA multicenter, descriptive, retrospective study was conducted evaluating 18 patients with self-limited epilepsy who presented with seizures with affective symptoms seen between April 2000 and April 2018 at eight Argentinian centers. ResultsEighteen patients had focal seizures with affective symptoms; all of them had affective symptoms characterized by sudden fright or terror and screaming. Seizures started with manifestations of sudden fright or terror manifested by a facial expression of fear; consciousness was mildly impaired in 15/18 patients.Eleven of the patients also had autonomic manifestations, such as pallor, sweating, and abdominal pain. In addition, four of these 11 patients had ictus emeticus and one also presented with unilateral deviation of the eyes and head.Speech arrest, salivation, glottal noises, and chewing or swallowing movements were observed in 2/18 patients at the onset of the affective seizures. Two others also had mild asymmetric dystonic seizures involving both hands and arms. Three patients had tonic deviation of the mouth involving the lips and tongue as well pharyngeal and laryngeal muscles, resulting in anarthria and drooling. Two patients had brief hemifacial focal clonic seizures. ConclusionAffective manifestations associated or not with motor and/or autonomic manifestations and associated with typical EEG features of the idiopathic focal epilepsies of childhood is a particular presentation of self-limited focal epilepsy in childhood.

Implicit cognitive flexibility in self-limited focal epilepsy of childhood: An HD-EEG study

Self-limited focal epilepsy of childhood (SFEC) is often related to mild impairments in several neuropsychological domains, including cognitive flexibility, which is generally considered a process requiring volition and attention. However, recent evidence showed that it can be implicitly adjusted exploiting simple ‘stimulus-response’ associations as for example, the probability of the stimulus occurrence. Here, we evaluated the capability to implicitly extract environmental patterns of regularities and use them to flexibly adjust proactive control motor control. We tested 21 children with epilepsy (total IQ > 80; 13 with Childhood epilepsy with centro-temporal spikes, 8 with Panayiotopoulos syndrome (PS); 5–13 years old) compared to a healthy age-matched control group (32 participants). We used the Dynamic Temporal Prediction (DTP) task to investigate how behavioral performance is implicitly shaped by the manipulation of the stimulus occurrence probability over time. We recorded EEG to identify neural markers to differentiate the two groups. SFEC group showed a reduction in accuracy (p = .0013) and response speed (p < .001) as well as an absence of response adjustment (p = .65) in relation to the implicit changes in stimulus probability occurrence, in comparison to the control group. The epilepsy group performance in the DTP showed a significant correlation with the phonemic fluency (r = −0.50) and the Perseverations index of the CPT test (r = 0.53). Finally, children with SFEC did not show the modulation of the contingent negative variation (CNV) evoked potential. Overall, children with SFEC showed poor implicit flexibility compared to a control group. This pattern is individually related to high-level executive function, suggesting to extend neuropsychological assessment to the implicit domain.

Self-limited focal epilepsy and childhood apraxia of speech with WAC pathogenic variants.

Heterozygous pathogenic WAC variants cause Desanto-Shinawi syndrome; affected patients have dysmorphic features, developmental impairment and behavioral abnormalities. Seizures are reported in one quarter, including tonic-clonic, absence, and febrile seizures. This study aimed to better understand the phenotypic spectrum of epilepsy and development in Desanto-Shinawi syndrome. We identified four children with seizures and pathogenic WAC variants, including two siblings. All had global developmental impairment with language affected most severely; two had diagnoses of childhood apraxia of speech and two had autism spectrum disorder. Seizure onset age ranged from six months to 14 years. Seizures always occurred from sleep and were focal impaired awareness with motor features in three patients, with one having bilateral tonic-clonic seizures of suspected focal onset. Two patients had spontaneous seizure resolution without treatment, and the remaining two were well-controlled on monotherapy. EEG was normal in two patients; one had focal right frontal spikes in drowsiness and sleep while the last had independent centrotemporal spikes from both hemispheres, activated in sleep. All patients had heterozygous truncating pathogenic WAC variants, with negative parental testing. The findings in this cohort of patients suggest that epilepsy in Desanto-Shinawi syndrome is usually focal and self-limited, and may fall within the epilepsy-aphasia spectrum.

A qualitative awake EEG score for the diagnosis of continuous spike and waves during sleep (CSWS) syndrome in self-limited focal epilepsy (SFE): A case-control study

PurposeTo determine whether awake EEG criteria can differentiate epileptic encephalopathy with continuous spike and waves during sleep (EE-CSWS) at the time of cognitive regression from typical, self-limited focal epilepsy (SFE). MethodsThis retrospective case-control study was based on the analysis of awake EEGs and included 15 patients with EE-CSWS and 15 age-matched and sex-matched patients with typical SFE. The EEGs were anonymised and scored by four independent readers. The following qualitative and quantitative EEG indices were analysed: slow-wave index (SLWI), spike-wave index (SWI), spike-wave frequency (SWF), long spike-wave clusters (CLSW) and EEG score (between grades 0 and 4). Sensitivity and specificity were assessed using receiver operating characteristic (ROC) curves and their reproducibility with a kappa test. ResultsBased on a highly sensitive cut-off, EE-CSWS patients were 8.4 times more likely than those with SFE to have an SLWI > 6%, 15 times more likely to have an SWI > 10 % and six times more likely to have a CLSW of ≥ 1 s. There was substantial agreement between readers (with kappa values of 0.64, 0.69 and 0.67). EE-CSWS patients were 13 times more likely to have an SWF of > 11 % and 149 times more likely to have an EEG score of ≥ 3 than typical SFE patients. Agreement about these ratings was almost perfect (kappa 0.91 and 0.86). ConclusionAn EEG score of ≥ 3 on a 20-min awake EEG differentiates typical SFE from EE-CSWS at the time of cognitive regression, with good reliability across readers with different levels of expertise.

Self-limited focal epilepsy decreased regional brain activity in sensorimotor areas.

The fractional amplitude of low-frequency fluctuation (fALFF) method was used to identify the regional brain activity deficits of self-limited focal epilepsy with centrotemporal spikes (SLFECS) relative to normal controls (NCs). A total of 21 SLFECS (10 females, 11 males; mean age, 8.57±1.5years) and 21 status-matched (age, sex, and education) NCs (10 females, 11 males; mean age, 8.76±2.19years) were recruited. The fALFF method was applied to identify SLFECS-related regional brain alterations. Receiver operating characteristic (ROC) curve was applied to identify the ability of these regional brain areas in distinguishing the SLFECS group from the NCs group. The relationships between the regional brain activity deficits and clinical features were evaluated by Pearson's correlation analysis. Self-limited focal epilepsy with centrotemporal spikes was associated with widespread regional brain activity alterations, including left cuneus with higher fALFF values, and bilateral striatum, bilateral precentral gyrus, ventral and dorsal pathway of sensory area, left dorsolateral prefrontal cortex, and left Rolandic area with lower fALFF values. ROC curve revealed excellent AUC value (0.964) of these areas in distinguishing the SLFECS group from the NCs group with high degree of sensitivity (90.5%) and specificity (95.2%). Intelligence quotient score positively correlated with the fALFF value in the left striatum (r=0.453, p=0.039). The fALFF parameter could be served as a potential biomarker to identify the SLFECS-related regional brain deficits in the sensorimotor cortex and their pathways, which may be the etiology of paresthesia in SLFECS.

Withdrawn: Self-limited focal epilepsy decreased regional brain activity in sensorimotor areas.

The fractional amplitude of low-frequency fluctuation (fALFF) method was used to identify the regional brain activity deficits of Self-limited focal epilepsy with centrotemporal spikes (SLFECS) relative to normal controls (NCs). Total of twenty-one SLFECS (10 females, 11 males; mean age, 8.57 ± 1.5 years) and twenty-one status-matched (age-, sex-, and education) NCs (10 females, 11 males; mean age, 8.76 ± 2.19 years) were recruited. The fALFF method was applied to identify SLFECS-related regional brain alterations. Receiver operating characteristic (ROC) curve was applied to identify the ability of these regional brain areas in distinguishing the SLFECS group from the NCs group. The relationships between the regional brain activity deficits and clinical features were evaluated by Pearson's correlation analysis. SLFECS was associated with widespread regional brain activity alterations, including left cuneus with higher fALFF values, and bilateral striatum, bilateral precentral gyrus, ventral and dorsal pathway of sensory area, left dorsolateral prefrontal cortex, and left Rolandic area with lower fALFF values. ROC curve revealed excellent AUC value (0.964) of these areas in distinguishing the SLFECS group from the NCs group with high degree of sensitivity (90.5%) and specificity (95.2%). Intelligence quotient score positively correlated with the fALFF value in the left striatum (r = 0.453, p = 0.039). The fALFF parameter could be served as a potential biomarker to identify the SLFECS-related regional brain deficits in the sensorimotor cortex and their pathways, which may be the etiology of paresthesia in SLFECS.

X-Linked Familial Focal Epilepsy Associated With Xp22.31 Deletion

BackgroundThe genetic basis for familial focal epilepsy is poorly understood, with most of the known genetic causes occurring via autosomal dominant inheritance. X-linked familial focal epilepsy has not been previously reported. MethodsWe reviewed our research database for cases of X-linked focal epilepsy. ResultsWe identified three boys with X-linked ichthyosis and focal epilepsy, including two maternal cousins. Age of seizure onset ranged from seven to 10 years, and all three patients had seizures that were relatively easily controlled. The epilepsy phenotype in all boys was consistent with self-limited focal epilepsy of childhood, most closely resembling childhood epilepsy with centrotemporal spikes. Brain magnetic resonance imaging was normal in two of the boys, with a third found to have a suspected focal cortical dysplasia. All three boys carried maternally inherited hemizygous Xp22.31 deletions (estimated size 0.9 to 1.66 Mb), affecting four to six genes. Of the affected genes, only STS has clear clinical relevance; deletions, and pathogenic variants in STS cause X-linked ichthyosis, although all patients described had only minor skin findings. ConclusionsThe findings in these patients illustrate that X-linked familial focal epilepsy can occur, although it is a rare entity. Although STS pathogenic variants are likely better categorized as an epilepsy risk factor, variants in this gene may partially explain the male predominance observed in specific epilepsy phenotypes, namely childhood epilepsy with centrotemporal spikes.