Electrical Status Epilepticus In Sleep Research Articles

Neurocognitive Profile and 18 F-Fluorodeoxyglucose Positron Emission Tomography Brain Imaging Correlation in Children with Electrical Status Epilepticus during Sleep.

Objective Electrical status epilepticus in sleep (ESES) is defined by near-continuous epileptiform discharges during sleep along with cognitive, behavioral, and/or imaging abnormalities. We studied the neurocognitive profile and their correlation with 18 F fluorodeoxyglucose positron emission tomography (FDG PET) brain abnormalities in children with ESES. Methods Fourteen children with ESES with normal magnetic resonance imaging (MRI) from March to December 2019 were included. The intelligence quotient (IQ) and child behavior checklist (CBCL) scores were estimated using validated scales, and FDG PET brain was done at the same point of time to look for cerebral metabolic defects which was compared with a control group. Results Fourteen patients with a mean age of 8.2 ± 2.7 years were analyzed. The average duration of epilepsy was 6 ± 2.8 years. The mean IQ was 72.4 ± 18.2 and mean CBCL score was 37.3 ± 11.8. There was negative correlation between IQ and CBCL ( r = -0.55, p < 0.001). The duration of epilepsy also showed negative correlation with IQ ( r = -4.75, p < 0.001). FDG PET scan showed predominant thalamic hypometabolism in 12 of 14 patients (85.7%) on visual analysis with multiple other hypometabolic cortical and subcortical regions in the brain. The quantitative analysis showed significant difference in metabolism of basal ganglion when compared with control group. The total number of hypometabolic regions seen in the brain showed moderate positive correlation with CBCL score but no significant correlation with the IQ of cases. Conclusion This study demonstrates functional impairment of cerebral cortical, basal ganglia, and thalamic hypometabolism in a cohort of ESES patients with normal structural MRI brain study. There was a moderate correlation of extent and pattern of cerebral hypometabolism with the neuropsychological status of the child and duration of epilepsy.

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.

Effects of altered excitation-inhibition imbalance by repetitive transcranial magnetic stimulation for self-limited epilepsy with centrotemporal spikes.

Patients with self-limited epilepsy with centrotemporal spikes (SeLECTS) with electrical status epilepticus in sleep (ESES) have generalized cognitive impairment, yet treatment options are limited. Our study aimed to examine the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) on SeLECTS with ESES. In addition, we applied electroencephalography (EEG) aperiodic components (offset and slope) to investigate the improvement of rTMS on the excitation-inhibition imbalance (E-I imbalance) in the brain of this group of children. Eight SeLECTS patients with ESES were included in this study. Low-frequency rTMS (≤1 Hz) was applied for 10 weekdays in each patient. To assess the clinical efficacy and changes in E-I imbalance, EEG recordings were performed both before and after rTMS. Seizure-reduction rate and spike-wave index (SWI) were measured to investigate the clinical effects of rTMS. The aperiodic offset and slope were calculated to explore the effect of rTMS on E-I imbalance. Five of the eight patients (62.5%) were seizure-free within 3 months after stimulation, with treatment effects decreasing with longer follow-ups. The SWI decreased significantly at 3 and 6 months after rTMS compared with the baseline (P = 0.0157 and P = 0.0060, respectively). The offset and slope were compared before rTMS and within 3 months after stimulation. The results showed a significant reduction in the offset after stimulation (P < 0.0001). There was a remarkable increase in slope after the stimulation (P < 0.0001). Patients achieved favorable outcomes in the first 3 months after rTMS. The ameliorative effect of rTMS on SWI may last up to 6 months. Low-frequency rTMS could reduce firing rates in neuronal populations throughout the brain, which was most pronounced at the site of stimulation. A significant reduction in the slope after rTMS treatment suggested an improvement in the E-I imbalance in the SeLECTS.

N°12 – Efficacy of steroids in seizure control and dipole stabilisation in drug resistant Electrical Status Epilepticus in Sleep due to structural cause

N°12 – Efficacy of steroids in seizure control and dipole stabilisation in drug resistant Electrical Status Epilepticus in Sleep due to structural cause

N°11 – Classification of Electrical Status Epilepticus in Sleep based on EEG patterns and spatiotemporal mapping of spikes

N°11 – Classification of Electrical Status Epilepticus in Sleep based on EEG patterns and spatiotemporal mapping of spikes

Electrical Status Epilepticus during Sleep: Risk Factors, Clinical Course, and Treatment Approaches

Abstract Background The efforts of clinicians are focused on determining the predictors for electrical status epilepticus in sleep (ESES) manifestation, due to the negative effect of ESES on cognition. Treatment approaches remain a leading problem because of therapeutic resistance. Objective We looked for potential risk factors for ESES manifestation and summarize the clinical course and therapeutic approaches in patients with idiopathic and symptomatic ESES. Patients and Methods We retrospectively reviewed the medical data of 51 children with idiopathic ESES and 20 children with symptomatic ESES. Results We observed an earlier age of seizure onset (p = 0.0002) and a higher percentage of cases with multiple seizures (p &lt; 0.00001) and with postictal paralysis (p &lt; 0.00001) in idiopathic ESES compared with childhood epilepsy with centrotemporal spikes. In the idiopathic ESES, the treatment consisted of corticosteroids in patients with permanent ESES remission and transient remission, levetiracetam (LEV) children with permanent ESES remission and transient, clonazepam (CZP) children with permanent ESES remission and transient, ethosuximide (ESM), and sulthiame. The patients with symptomatic ESES had more unfavorable evolution, as 19 children had persistent or relapsing ESES course. Conclusion We consider the earlier age of seizure onset (below 5 years) and the presence of multiple seizures and postictal paresis as risk factors for ESES manifestation. ESES is characterized by a significant therapeutic resistance, especially in the group of symptomatic cases. Good results are observed with LEV, ESM, CZP, and steroids.

Evaluation of Thiol-Disulfide Homeostasis with Electrical Status Epilepticus in Slow Sleep (ESES).

Electrical status epilepticus in sleep (ESES) is an epileptic syndrome specific to childhood and has a broad clinical spectrum that included seizures, behavioral/cognitive impairments, and motor neurological symptoms. Antioxidants are seen as promising neuroprotective strategies for the epileptic state by combating the harmful effects of excessive oxidant formation in mitochondria. This study aims to evaluate the thiol-disulfide balance and to determine whether it can be used in the clinical and electrophysiological follow-up of patients with ESES, especially in addition to the electroencephalography (EEG) examination. The study included 30 patients, aged 2-18 years and diagnosed with ESES in the Pediatric Neurology Clinic of the Training and Research Hospital and a control group of 30 healthy children. Total thiol, native thiol, disulfide, and ischemia-modified albumin (IMA) levels were measured, and disulfide-thiol ratios were calculated for both groups. Native thiol and total thiol levels were significantly lower and IMA level and disulfide-native thiol percentage ratio were significantly higher in the ESES patient group than in the control group. Serum thiol-disulfide homeostasis is an accurate marker of oxidative stress in ESES, and standard and automated measures of thiol-disulfide balance as an indicator of oxidative stress showed a shift toward oxidation in ESES patients in this study. The negative correlation between spike-wave index (SWI) and thiol levels, and serum thiol-disulfide levels suggest that they can be used as biomarkers for follow-up of patients with ESES in addition to EEG. IMA can also be used for long-term response to monitoring purposes at ESES.

Is sleep captured during a standard daytime EEG sufficient to diagnose Electrical Status Epilepticus in Sleep.

Electrical Status epilepticus of sleep (SES) is an EEG pattern where there is significant activation of epileptiform activity in NREM sleep. A spike wave index (SWI) of>80-85% is often labelled as typical SES. We aimed to explore if sleep during a standard daytime-EEG, as compared an overnight-EEG, was adequate to diagnose ESES. Ten children with daytime and overnight studies suggestive of SES were audited. SWI and Spike Wave Density (SWD) were calculated for 5-minute epochs of wake in the daytime and overnight study, as well daytime-EEG sleep and first and last NREM cycle in the overnight-EEG. SWI in daytime NREM was not significantly different from SWI in the first sleep cycle of the overnight study. SWI in the last sleep cycle was significantly lower than the first sleep cycle in the overnight-EEG. SWD was significantly higher in the first sleep cycle in the overnight-EEG than the daytime sleep and the last NREM cycle. SES may be diagnosed in NREM sleep from a daytime-EEG study. Larger studies are needed to explore the significance of the disparity between SWI and SWD in the first and last NREM cycles in the overnight study.

Corpus callosum thickness: A predictive factor for the first drug efficiency of self-limited epilepsy with centrotemporal spikes (selects)?

ObjectiveTo investigate the existence of a possible linkage between the thickness of corpus callosum (CC) regions and the first antiepileptic drug response in patients with Selects. Materials and methodsCC thickness of 68 patients with Selects and 42 healthy controls between 4 and 12 years of age were measured using brain magnetic resonance imaging (MRI). Clinical and EEG features of newly diagnosed Selects patients were recorded. Patients were divided into two groups: good-response (patients without seizures within 24 weeks) and poor-response (patients with ≥ 1 seizure within 24 weeks). Thickness of CC was compared between patients (good-response and poor-response groups).and healthy controls. ResultsThe thicknesses of genu and isthmus were significantly reduced in the Selects group than healthy controls. Isthmus and splenium were significantly thinner in poor responders than those in the good-response group (p = 0.005 and p < 0.001, respectively). The total number of seizures was negatively correlated with the thickness of the body, isthmus, and splenium (p < 0.001). There was no significant difference in CC thickness of the children with and without electrical status epilepticus in sleep (ESES). The thickness of the isthmus and splenium were significantly thinner in patients receiving ≥ 2 antiepileptic drugs (p = 0.002 and p = 0.001, respectively). ConclusionsOur study highlights the notable differences in areas of CC in Selects patients. These changes may help uncover the underlying cause of seizure recurrence and antiepileptic drug (AED) response. Different thinner parts of CC may be a protective mechanism to prevent seizure spread to other brain regions. CC thickness can be used as a new radiologic biomarker for predicting first AED response and seizure recurrence in Selects patients.

Classification of electrical status epilepticus in sleep based on EEG patterns and spatiotemporal mapping of spikes

We firstly aimed to describe and classify EEG patterns in electrical status epilepticus in sleep (ESES), and secondly subclassify EEG patterns based on analysis of spikes using spatio-temporal mapping and electrical source analysis. Overnight EEGs (minimum: eight hours) of 30 children, aged 2-12 years, with ESES (spike-wave index: at least 50%) were selected. Average reference montage was used for dipole analysis and mapping. The location and orientation of the dipoles were determined by mapping positive and negative poles and applying the rules of mapping. The onset and propagation of the spikes and the latency between the two hemispheres (for bisynchronous spikes) were determined (based on source analysis using BESA research 7.1). (1) ESES was classified as “generalised” (80%) and focal (20%) patterns; (2) the bisynchronous subtype in the “generalised” pattern was due to apparently synchronous bilateral activation of spikes (with lead-in of 20-60 ms from one hemisphere) with a tangential/oblique dipole (source analysis localised these spikes to around the peri-rolandic cortex); (3) the classic description of ESES spikes as “diffuse” spikes with bifrontal maxima is a misinterpretation using the 10-20 EEG system .Using voltage mapping and source analysis, cortical activation in the rolandic cortex was identified which imparts diffuse frontal negativity and parieto-occipital positivity; (4) ESES spikes showed intraspike and interspike dipole instability and the orientation of dipoles changed due to local spike propagation around the source and into the depth of the sulcus (which we refer to herein as “dancing dipoles”); and (5) focal ESES were classified as parietal, occipital and temporo-occipital patterns;a frontal ESES pattern was not seen. Based on detailed mapping and source analysis of ESES, we have successfully reinterpreted various misconceptions in the literature. We have simplified the interpretation of complicated EEG patterns by extracting the primary and propagated sources which aid the classification of ESES. As the dipole is always stable in self-limited childhood epilepsy with centrotemporal spikes, we believe that the phenomenon of an intrinsically unstable dipole is a reliable qualitative EEG marker of ESES.

Are Interictal Discharges Associated with Neuronal Cell Loss in Electrical Status Epilepticus in Sleep?

Neuron-specific enolase is an established biomarker of neuronal damage. This study aimed to reveal the relationship between serum neuron-specific enolase level and continuous interictal discharges in a group of encephalopathy with electrical status epilepticus in sleep patients for the first time and determine whether there is a neuronal cell loss or damage. We analyzed serum neuron-specific enolase levels in patients with an electrical status epilepticus in sleep pattern on their electroencephalographs with age- and sex-matched control subjects. Patients with a spike-wave index of at least 50% and acquired neuropsychological regression were included in the study. Magnetic resonance imaging of all electrical status epilepticus in sleep patients and control subjects included in the study was within normal limits. Neuron-specific enolase is measured by the enzyme-linked immunosorbent assay kit based on the sandwich technique. In this study, 14 patients diagnosed with electrical status epilepticus in sleep and 21 healthy controls were included. The median age of electrical status epilepticus in sleep patients was 7.1 years (min-max: 4.5-10.7 years) and 7.7 years (min-max: 3.2-14 years) in the control subjects. According to the results of serum neuron-specific enolase measurements, the mean ± standard deviation level of neuron-specific enolase was 7.61 ± 3.19 ng/dL for the electrical status epilepticus in sleep group and 6.93 ± 2.55 ng/dL for the control group. Serum neuron-specific enolase levels between electrical status epilepticus in sleep patients and the control group were not statistically significant (P = .749). No significant difference was observed in serum neuron-specific enolase levels between electrical status epilepticus in sleep patients and control subjects. Our results may indicate that frequent interictal discharges do not result in neuronal cell loss or damage in electrical status epilepticus in sleep patients.

Are Interictal Discharges Associated with Neuronal Cell Loss in Electrical Status Epilepticus in Sleep?

Neuron-specific enolase is an established biomarker of neuronal damage. This study aimed to reveal the relationship between serum neuron-specific enolase level and continuous interictal discharges in a group of encephalopathy with electrical status epilepticus in sleep patients for the first time and determine whether there is a neuronal cell loss or damage. We analyzed serum neuron-specific enolase levels in patients with an electrical status epilepticus in sleep pattern on their electroencephalographs with age- and sex-matched control subjects. Patients with a spike-wave index of at least 50% and acquired neuropsychological regression were included in the study. Magnetic resonance imaging of all electrical status epilepticus in sleep patients and control subjects included in the study was within normal limits. Neuron-specific enolase is measured by the enzyme-linked immunosorbent assay kit based on the sandwich technique. In this study, 14 patients diagnosed with electrical status epilepticus in sleep and 21 healthy controls were included. The median age of electrical status epilepticus in sleep patients was 7.1 years (min-max: 4.5-10.7 years) and 7.7 years (min-max: 3.2-14 years) in the control subjects. According to the results of serum neuron-specific enolase measurements, the mean ± standard deviation level of neuron-specific enolase was 7.61 ± 3.19 ng/dL for the electrical status epilepticus in sleep group and 6.93 ± 2.55 ng/dL for the control group. Serum neuron-specific enolase levels between electrical status epilepticus in sleep patients and the control group were not statistically significant (P = .749). No significant difference was observed in serum neuron-specific enolase levels between electrical status epilepticus in sleep patients and control subjects. Our results may indicate that frequent interictal discharges do not result in neuronal cell loss or damage in electrical status epilepticus in sleep patients.

Neurobehavioral deterioration associated with sleep-augmented epileptiform abnormalities: A steroid responsive state in children

ObjectiveRetrospective case record analysis of children with Neurobehavioral Deterioration associated with Sleep-augmented Epileptiform abnormalities (NDSE). MethodsHospital records of children with NDSE (July, 2015 through December, 2016) were analyzed. Children were categorized as: Encephalopathy with electrical status epilepticus in sleep (ESES) if sleep EEG Spike-wave-Index (SWI) was ≥50% and sleep-induced epileptiform activity (SIEA)-related cognitive dysfunction if SWI ≥25% but <50%. Demography, neurobehavior profile (IQ/SQ and behavior using validated psychometric tools), etiology, investigations and treatment details were documented. Outcome assessment was based on three-month follow-up records. ResultsEighteen children with NDSE {12 boys; median age at diagnosis: 7.5 years (IQR: 6–10 years); SIEA (7); ESES (11)} were included. Etiology was structural (23%) and presumed genetic (77%). All children received intravenous-methylprednisolone pulse followed by oral steroids for eight weeks. Electroencephalography of children with SIEA was partly organized with median SWI of 40% (IQR 35, 42), with anterior-predominant epileptiform abnormalities and less apparent secondary synchronization. Children with ESES had a disorganized EEG background with median SWI of 80% (IQR 66, 95). Both SIEA and ESES groups had a similar neurobehavior profile.Behavior scores improved in 6/8 children with ESES and 5/7 in SIEA post steroids. In both the groups, median SWI improved (to <5% in SIEA, 45% in ESES). Mild improvement in IQ/SQ was also noted {SIEA [Median (IQR): 3 (1.6, 4.3)]; ESES [Median (IQR): 3.8 (2.8, 7)]}. ConclusionThe study supports the fact that SWI >50% in the nap EEG is not mandatory for the diagnosis of ESES, thus it should not be a constraint for steroid treatment.

Progression of alternating hemiplegia of childhood‐related focal epilepsy to electrical status epilepticus in sleep with reversible encephalopathy

Mutations in the ATP1A3 gene (which encodes the main α subunit in neuronal Na+/K+-ATPases) cause various neurological syndromes including alternating hemiplegia of childhood. This rare disorder is characterized by paroxysmal episodes of hemiplegia, dystonia, oculomotor abnormalities, and occasionally developmental regression. Approximately 50% of alternating hemiplegia of childhood patients also have epilepsy, which is either focal or generalized. Seizures are often drug resistant. We report a 10-year-old girl with the D801N ATP1A3 mutation and alternating hemiplegia of childhood who manifested with drug-resistant focal seizures as an infant and throughout childhood. At the age of about10.5 years, her epilepsy evolved into electrical status epilepticus in sleep with generalized discharges. These changes coincided with developmental regression consistent with epileptic encephalopathy. Additionally, MRI and MR spectroscopy showed new cortical atrophy and markedly depressed N-acetyl aspartate peaks compared to previous normal studies. Electrical status epilepticus in sleep resolved after medication adjustments. She, now, only four months after her diagnosis of electrical status epilepticus in sleep, has regained most of the skills that were lost only a few months earlier. Our observations document that alternating hemiplegia of childhood can result in the above-described unique features; particularly, progression of focal epilepsy to electrical status epilepticus in sleep with generalized features and reversible epileptic encephalopathy.

The Spike-Wave Index of the First 100 Seconds of Sleep Can Be a Reliable Scoring Method for Electrographic Status Epilepticus in Sleep.

Electrical status epilepticus in sleep (ESES) is an electrographic pattern in which interictal epileptiform activity is augmented by the transition to sleep, with non-rapid eye movement sleep state characterized by near-continuous lateralized or bilateral epileptiform discharges. The aim of this study was to measure the reliability of the spike-wave index (SWI) of the first 100 seconds of sleep as a tool for the diagnosis of ESES. One hundred forty studies from 60 unique patients met the inclusion. Two neurophysiologists calculated the SWI of the first 100 seconds of spontaneous stage II non-rapid eye movement sleep. This was compared with the SWI of the first 5 minutes of non-rapid eye movement sleep and the cumulative SWI of three 5-minute bins of sleep. Agreement between the three SWI methods were analyzed using several statistical tools and methods. Using an SWI of 50% as a diagnostic cutoff, 57% of records had a diagnosis of ESES based on the first 100 seconds of sleep. Fifty-four percent of records had a diagnosis of ESES based on the method of using the SWI of three bins. This resulted in a diagnostic accuracy of 92%, sensitivity of 96%, and specificity of 88%. Positive predictive values of children diagnosed with ESES using the first 100 seconds of sleep, compared with 3 combined bins, was determined to be 90% and a negative predictive value was determined to be 95%. This analysis confirmed the diagnostic accuracy of using the SWI of the first 100 seconds of sleep and the cumulative total of three 5-minute bins.

Does Electrical Status Epilepticus in Sleep Adversely Affect Language in Self-Limiting Focal Epilepsies of Childhood?

The electrical status epilepticus in sleep (ESES) accompanies a wide spectrum of focal and generalized epilepsies, which manifest with cognitive-linguistic regression. Both ESES and language impairment can be seen in self-limited focal epileptic syndromes of childhood (SFEC). The association between the presence of ESES pattern on the EEG and the severity of the language impairment has not been adequately clarified. Twenty-eight SFEC cases without intellectual and motor disabilities and 32 healthy children were recruited. Cases with active ESES (A-ESES, n=6) and without ESES pattern on EEG (non-ESES, n=22) were compared in terms of clinical features and linguistic parameters by both standard and descriptive assessment tools. The only significantly different clinical feature in the A-ESES group was the increased prevalence of polytherapy. While most of the linguistic parameters were impaired in A-ESES and non-ESES groups compared to healthy controls, A-ESES patients differed from non-ESES patients only in terms of decreased complex sentence production, which was assessed by narrative analysis. A-ESES patients also showed trends toward producing lower numbers of words, nouns, verbs, and adverbs during narrative analysis. There were no differences among patients under polytherapy and monotherapy in terms of these language parameters. Our results show that ESES increases the negative effect of chronic epilepsy on complex sentence and word production. Linguistic distortions that are not reflected in objective tests can be detected by narrative tools. Complex syntactic production obtained by narrative analysis is an important parameter that extensively characterizes language skills in school-age children with epilepsy.

P.101 Response to high dose nocturnal diazepam in children with ESES

Background: To assess the response to high dose daily nocturnal diazepam (HDD) in children with encephalopathy associated with electrical status epilepticus in sleep (ESES). Methods: A prospective cohort of patients (4-12 years), newly diagnosed with ESES, initiated on the first course HDD, was followed for ≤ 1-year. Sleep EEG scores (SES) pre and post HDD were evaluated. An EEG grading system based on both sleep spike wave index (sSWI) (Grade: 1-4) and distribution of epileptiform discharges (Grade: 0-4) was used and summed to yield an aggregate SES (ASES) (Grade: 1-8). Results: Eighteen eligible children (M:F 12:6; median age, 7.6 years) were initiated on first course HDD (median, 0.5 mg/kg/d). sSWI decreased from 85.7% (mean, SD 13.9) to 32.6% (mean, SD 37.1) at subsequent EEG (95% CI = -70.60- -35.62; p &lt; 0.001). ASES decreased from 6.5 (SD 1.3) to 3.1 (SD 1.9) (95% CI = -4.17- -2.60; p &lt; 0.001). EEG relapse after a period of improvement occurred in 10 children. Minimal response to HDD occurred in 2 children. Five patients manifested mild side effects; behavior (2), hyperactivity (2), and lethargy (1). Conclusions: HDD safely and significantly reduces both SWI and aggregate sleep EEG score in children with ESES.

Electrical status epilepticus in sleep: The role of thalamus in etiopathogenesis

PurposeIn patients diagnosed with epilepsy, decreased ratio of N-acetyl aspartate to creatine (NAA/Cr) measured in magnetic resonance spectroscopy (MRS) has been accepted as a sign of neuronal cell loss or dysfunction. In this study, we aimed to determine whether a similar neuronal cell loss is present in a group of encephalopathy with electrical status epilepticus in sleep (ESES) patients MethodsWe performed this case-control study at a tertiary pediatric neurology center with patients with ESES. Inclusion criteria for the patient group were as follows: 1) a spike-wave index of at least 50%, 2) acquired neuropsychological regression, 3) normal cranial MRI. Eventually, a total of 21 patients with ESES and 17 control subjects were enrolled in the study. MRI of all control subjects was also within normal limits. 3D Slicer program was used for the analysis of thalamic and brain volumes. LCModel spectral fitting software was used to analyze single-voxel MRS data from the right and left thalamus of the subjects. ResultsThe mean age was 8.0 ± 1.88 years and 8.3 ± 1.70 years in ESES patients and the control subjects. After correcting for the main potential confounders (age and gender) with a linear regression model, NAA/Creatine ratio of the right thalamus was significantly lower in the ESES patient group compared to the healthy control group (p = 0.026). Likewise, the left thalamus NAA/Cr ratio was significantly lower in the ESES patient group than the healthy control group (p = 0.007). After correcting for age and gender, right thalamic volume was not statistically significantly smaller in ESES patients than in healthy controls (p = 0.337), but left thalamic volume was smaller in ESES patients than in healthy controls (p = 0.024). ConclusionIn ESES patients, the NAA/Creatine ratio, which is an indicator of neuronal cell loss or dysfunction in the right and left thalamus, which appears regular on MRI, was found to be significantly lower than the healthy control group. This metabolic-induced thalamic dysfunction, which was reported for the first time up to date, may play a role in ESES epileptogenesis.

The spectrum of epilepsy in children with 15q13.3 microdeletion syndrome

PurposeTo further define the epilepsy phenotype in a cohort of children with 15q13.3 microdeletion syndrome. MethodsWe retrospectively reviewed the phenotypic spectrum of all children aged < 18 years with epilepsy and 15q13.3 microdeletion syndrome. ResultsThirteen children were included, 69% were female. The median age of children in the cohort was 12 years (age range: 3 years-15 years). Median age at seizure onset was 4 years. Eleven children (85%) had intellectual disability. Nine of 13 children (69%) had a history of typical absence seizures with median age of onset at 5 years (2 had absence status epilepticus). Thirty-one percent (4/13) had focal with impaired awareness non-motor onset seizures. ILAE recognized absence epilepsy syndromes were diagnosed in 6/13 (46%). The remainder were classified as having genetic generalized epilepsies with overlap clinical features, combined or focal epilepsies. Electroencephalogram in the cohort showed generalized (85%) and focal epileptiform discharges (62%) and posterior dominant rhythm slowing (33%). One child had electrical status epilepticus of sleep. Neuroimaging was performed in 5 children (38%) and revealed abnormal findings in 3. Seizures were drug resistant in a third of the cohort. Valproate resulted in seizure freedom in 5 (42%). Oxcarbazepine caused clinical worsening in one child with combined seizure types. Two children tried cannabidiol and one tried the ketogenic diet; neither was effective. ConclusionsThe epilepsy phenotype in children with 15q13.3 microdeletion syndrome is defined by childhood onset absence seizures, and may have atypical features such as, early onset absences, persistence into adolescence, status epilepticus, intellectual disability and treatment resistance. Focal seizures and focal EEG findings may be observed and should be treated cautiously, given the possibility of combined seizure types. Valproate appeared effective, although other treatments must be explored further.

IL1RAPL1 Gene Deletion in a Female Patient with Developmental Delay and Continuous Spike-Wave during Sleep

AbstractInterleukin-1 receptor accessory protein-like 1 (IL1RAPL1) encodes a protein that is highly expressed in neurons and has been shown to regulate neurite outgrowth as well as synapse formation and synaptic transmission. Clinically, mutations in or deletions of IL1RAPL1 have been associated with a spectrum of neurological dysfunction including autism spectrum disorder and nonsyndromic X-linked developmental delay/intellectual disability of varying severity. Nearly all reported cases are in males; in the few reported cases involving females, the clinical presentation was mild or the deletion was identified in phenotypically normal carriers in accordance with X-linked inheritance. Using genome-wide microarray analysis, we identified a novel de novo 373 kb interstitial deletion of the X chromosome (Xp21.1-p21.2) that includes exons 4 to 6 of the IL1RAPL1 gene in an 8-year-old girl with severe intellectual disability and behavioral disorder with a history of developmental regression. Overnight continuous video electroencephalography revealed electrical status epilepticus in sleep (ESES). This case expands the clinical genetic spectrum of IL1RAPL1-related neurodevelopmental disorders and highlights a new genetic association of ESES.