Epilepsy and Sleep in the ATR-X Syndrome

Background This study explores the prevalence, clinical characteristics, and treatment of epilepsy and sleep disorders in α thalassemia mental retardation (ATR-X) syndrome. Design In this cross-sectional study, 37 participants with ATR-X syndrome aged 1.8 to 44 years were studied using a customized epilepsy questionnaire, review of electroencephalography (EEG) findings, the modified Sleep Questionnaire of Simonds and Parraga and 2-week sleep diary. Results Eleven participants had a clinical diagnosis of generalized epilepsy (29.7%). Seizure types were generalized tonic-clonic seizures, absences, and myoclonia. Interictal EEG recordings in participants with GTCS showed no epileptic discharges in 78%. Similarly, EEG recordings during myoclonia and absences often demonstrated no epileptic discharges. Sleep problems (difficulty falling or maintaining sleep, and early awakening) were reported in 70%. Participants with reported sleep problems went to bed earlier (p = 0.027) and had a lower sleep efficiency (p < 0.01) than participants without sleep problems, but as a group they both had a sufficient total sleep time (9 hours and 52 minutes vs. 10 hours and 55 minutes). Sixteen participants (43.2) used medication to improve sleep (predominantly melatonin n = 10), being effective in only two. Conclusion One-third of participants with ATR-X syndrome had a clinical diagnosis of epilepsy, but the absence of EEG abnormalities in suspected epileptic seizures questions this diagnosis in these patients. EEG recording during seizure like symptoms is warranted before making an epilepsy diagnosis. Seventy percent experienced sleep problems, although total sleep time was normal in most participants. Long bedtimes might have a negative influence on sleep efficiency.

P.103 Midline Spikes and Intractable Seizures in Pediatric Epilepsy

Background: Epileptic discharges localized to the midline vertex are rare. However, they have been associated with intractable seizures and severe long-term consequences in the developing brain. Our study aimed to understand the etiology of pediatric midline seizures and define post-surgical seizure outcomes. Methods: We reviewed charts, electroencephalography (EEG), and neuroimaging studies of ten pediatric patients with epileptic discharges localized to the midline vertex in the Comprehensive Epilepsy Program. The seizures were classified according to the International League Against Epilepsy criteria, patient age, sex, neuroimaging results, seizure etiology and outcomes were obtained. Results: Age of seizure onset was within the first 10 years of life in 90% of patients, with focal seizures being the most prevalent. Focal cortical dysplasia (FCD) was the most common etiology present in 50% of patients. These children had normal neuroimaging studies and intractable epilepsy. However, seizure freedom was achieved following surgical resection of the epileptogenic zone. Conclusions: We demonstrated that patients with midline epileptic discharges are associated with intractable focal seizures and early seizure onset. Despite normal neuroimaging reports, FCD was the most common pathology. Thus our study suggests early localization and resection of the epileptogenic zone may be beneficial for achieving seizure freedom in children with this electroclinical syndrome.

Electroencephalogram Abnormalities and Epilepsy in Autism Spectrum Disorders: Clinical and Electroencephalogram Findings

It has been known for several decades that epilepsy and autism spectrum disorders (ASD) are related to each other. Epilepsy frequently accompanies ASD. The purpose of this study was to investigate relationship between clinical and electroencephalogram (EEG) findings in ASD patients and to identify EEG characteristics that may create a disposition to epilepsy in ASD by examining differences in clinical and EEG findings between patients diagnosed with ASD without epilepsy and ASD with epilepsy. A total of 102 patients aged 2 to 18 years and diagnosed with ASD based on Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnostic criteria between January 2017 and June 2019 were included in the study. Patients were assigned into two groups: (1) ASD with epilepsy and (2) ASD without epilepsy. Clinical findings were retrieved from patients' files, and EEG findings from first EEG records in the EEG laboratory at the time of diagnosis. EEG findings were defined as central, parietal, frontal, temporal, or generalized, depending on the location of rhythmic discharges. The incidence of epilepsy in our ASD patients was 33.7% and that of febrile convulsion was 4%. Generalized motor seizures were the most common seizure type. Epileptic discharges most commonly derived from the central and frontal regions. These abnormalities, especially frontal and central rhythmic discharges, may represent a precursor for the development of epilepsy in ASD patients.

Case Report: Hypopituitarism Presenting With Nonconvulsive Status Epilepticus

Introduction: Hypopituitarism is defined as one or more partial or complete pituitary hormone deficiencies. Nonconvulsive status epilepticus (NCSE) refers to a state of continuous or repetitive seizures without convulsions. In this paper, we review a case of an old female patient with hypopituitarism who presented with NCSE, which is rare in the clinic.Case Report: This paper describes a 67-year-old female patient with hypopituitarism who presented as NCSE. She had surgical resection of pituitary tumor half a year before the seizures and did not get regular hormone replacement therapy. She presented general convulsive status epilepsy as the initial symptom and got sedation and antiepileptic drug in the emergency room. The seizure was terminated but the patient fell in coma in the following days. The patient had magnetic resonance imaging (MRI) and other inspects, and EEG showed epileptic discharges. Combining these clinical symptoms and examinations, we made the diagnosis of NCSE. Finally, she regained consciousness after the treatment with diazepam.Conclusion: This case report and literature review investigated the possible mechanism of hypopituitarism presenting with NCSE.

Effect of the compound GIZH -290 and levetiracetam on epileptic activity in rat brain structures on EEG models of bemegrid-induced seizures

The effect of levetiracetam (a derivative of 4-phenylpyrrolidone) and its original analog, the compound GIZH-290, on primary generalized epileptic activity (EpA) in rat brain structures (sensorimotor cortex, dorsal hippocampus-CA3 field and lateral hypothalamus field) on EEG models of bemegridinduced seizures was studied. It was found that EpA, after the introduction of bemegrid, appears in 1–2 minutes in the form of prolonged generalized high-amplitude discharges and is registered within 3 hours. GIZH-290 (5 mg/kg, intraperitoneal, 15 minutes after bemegrid) causes a significant (p < 0.05) decrease in the number of epileptic discharges in the cortex and at the level of the trend in the hippocampus, which is accompanied by a decrease in the amplitude of the Epi-discharges. Levetiracetam at a dose of 200 mg / kg does not significantly change the severity of paroxysmal activity (the number of convulsive discharges and their duration) caused by bemegrid.

Case Report: A Case of Eyelid Myoclonic Status With Tonic–Clonic Seizure and Literature Review

Eyelid myoclonus with or without absence epilepsy is a rare and usually misdiagnosed disease in the neurology department. It is an idiopathic general epileptic syndrome, the onset period is 6–8 years, and is more common in girls. It is characterized by rapid abnormal eye blinking, accompanied by upward rolling of the eye and slight backward movement of the head, with eye closure sensitivity and photosensitivity. The seizure is frequent and short, dozens or even hundreds of times a day; a small number of patients may have eyelid myoclonus status. We report a patient who visits the hospital for the first time with eyelid myoclonic problem; the patient continued to wink the eyes, eye rolled up, and backward movement of the head, accompanied by impairment of consciousness. Video electroencephalography (VEEG) suggests continued spike slow-wave, polyspike slow-wave. After the patient had 2, 4, 6, 8, 10, 12, and 14 Hz of intermittent photic stimulation (IPS), her seizures and epileptic discharges reduced or stopped. Seven min after giving stimulation at 20 Hz, the child developed an occipital-initiated tonic–clonic seizure, which demonstrated that after sufficient IPS stimulation, the occiput cortex became excited and initiated a brain network, leading to diffuse brain discharge and tonic–clonic seizures. At 1 h after onset, the child developed a nonconvulsive state, with impairment of consciousness despite no eyelid myoclonic movements, and VEEG suggested a large number of epileptic discharges. After 10 min of administrating midazolam, the patient's EEG immediately became normal, and the patient regained consciousness. Therefore, this paper presents an eyelid myoclonus status patient with occipital origin seizure, we recorded the whole course of the disease and the treatment effect, and reviewed the literature accordingly.

Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications

We report detailed functional analyses and genotype-phenotype correlations in 433 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel NaV1.6. Five different clinical subgroups could be identified: 1) Benign familial infantile epilepsy (BFIE) (n=17, normal cognition, treatable seizures), 2) intermediate epilepsy (n=36, mild ID, partially pharmacoresponsive), 3) developmental and epileptic encephalopathy (DEE, n=191, severe ID, majority pharmacoresistant), 4) generalized epilepsy (n=21, mild to moderate ID, frequently with absence seizures), and 5) affected individuals without epilepsy (n=25, mild to moderate ID). Groups 1-3 presented with early-onset (median: four months) focal or multifocal seizures and epileptic discharges, whereas the onset of seizures in group 4 was later (median: 39 months) with generalized epileptic discharges. The epilepsy was not classifiable in 143 individuals. We performed functional studies expressing missense variants in ND7/23 neuroblastoma cells and primary neuronal cultures using recombinant tetrodotoxin insensitive human NaV1.6 channels and whole-cell patch clamping. Two variants causing DEE showed a strong gain-of-function (GOF, hyperpolarising shift of steady-state activation, strongly increased neuronal firing rate), and one variant causing BFIE or intermediate epilepsy showed a mild GOF (defective fast inactivation, less increased firing). In contrast, all three variants causing generalized epilepsy induced a loss-of-function (LOF, reduced current amplitudes, depolarising shift of steady-state activation, reduced neuronal firing). Including previous studies, functional effects were known for 165 individuals. All 133 individuals carrying GOF variants had either focal (76, groups 1-3), or unclassifiable epilepsy (37), whereas 32 with LOF variants had either generalized (14), no (11) or unclassifiable (5) epilepsy; only two had DEE. Computational modeling in the GOF group revealed a significant correlation between the severity of the electrophysiological and clinical phenotypes. GOF variant carriers responded significantly better to sodium channel blockers (SCBs) than to other anti-seizure medications, and the same applied for all individuals of groups 1-3. In conclusion, our data reveal clear genotype-phenotype correlations between age at seizure onset, type of epilepsy and gain- or loss-of-function effects of SCN8A variants. Generalized epilepsy with absence seizures is the main epilepsy phenotype of LOF variant carriers and the extent of the electrophysiological dysfunction of the GOF variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Our pharmacological data indicate that SCBs present a therapeutic treatment option in early onset SCN8A-related focal epilepsy.