Primary Headache Is Related to Reduced Health-Related Quality of Life in Children with Epilepsy

Headache is a frequent comorbidity in patients with epilepsy. Data are sparse regarding the distribution of headache types in children with epilepsy (CWE). We aimed to assess the prevalence of primary headache types and their influence on health-related quality of life (QoL) in CWE. CWE filled out a validated headache questionnaire to assess migraine (MIG), tension-type headache (TTH), trigeminal–autonomic cephalalgia (TAC), or, if the criteria were not fulfilled, non-classifiable headache (NCH). QoL was measured using both patient and parent versions of a validated questionnaire. Of 119 CWE (59 female; 11.5 ± 3.1 y), headache was found in 46 (38.7%). Sixteen (34.8%) patients showed MIG, 9 (19.6%) patients TTH, and 21 (45.7%) patients described NCH. More girls reported headache (χ2 = 5.4, p = 0.02) when compared to boys. Overall, QoL was reduced in patients with headache from both the patients’ and parents’ points of view (70.8% [39.6; 87.5] vs. 77.0% [46.9; 95.8], p = 0.002; 71,9% [33.3; 87.5] vs. 78,1% [54.2; 95.8], p = 0.003). Headache is common among CWE with MIG as the most prevalent primary headache type and higher rates in female patients. Importantly, patients and their parents perceive a reduced overall QoL when suffering from headache

Monitoring Glucose Concentrations in Children with Epilepsy on a Ketogenic Diet

Ketogenic diet (KD) and pulsatile dexamethasone therapy (PDT) are commonly used in the treatment of children with drug resistant epilepsy. Potential side effects of the KD are hypoglycemia, whereas PDT might lead to hyperglycemia. One practical option to measure glucose concentrations regularly is the flash glucose monitoring system (FGM). In this single-center study in Germany, two pediatric patients with epilepsy (age: 6.0 and 6.8 years) received FGM from the beginning of the KD over six months, in the year 2020, and one patient (9.8 years) was observed for one month on PDT and switched to the KD thereafter. Glucose concentrations were measured by using an FGM system and capillary blood measurement. Seizure frequency, changes in cognition, motor performance, social behavior, and sleep quality were evaluated. The mean hypoglycemia rate per day (65 mg/dL and lower) declined significantly in patient 1 and 2 after three months. Patient 3 showed in total seven hyperglycemic events during PDT. Patient 1 became seizure free. Improvement of attention and memory performance were reported. FGM during the KD as a treatment for drug resistant epilepsies in childhood is a practical option to explore and to avoid hypoglycemia during the KD and hyperglycemia during PDT

Pulsatile corticoid therapy reduces interictal epileptic activity burden in children with genetic drug‐resistant epilepsy

Abstract Objective Corticosteroids and adrenocorticotropic hormone (ACTH) are the therapy of choice to treat infantile spasms. However, systematic studies about their use in other types of childhood epilepsies remain rare and ACTH can have serious side effects. This study compares the interictal epileptic activity (IEA) burden (% of electroencephalography (EEG) time with IEDs) in children with genetic drug‐resistant epilepsy before and after a standardized treatment with pulsatile corticoid therapy (PCT). Methods Children with drug‐resistant epilepsy underwent a standardized protocol for PCT with cycles of high‐dose dexamethasone (20 mg/m2 body surface) intravenously. Patients were hospitalized for 3 days per PCT cycle and EEGs were obtained before initiation of treatment (baseline) and during the hospitalization around the time of every second cycle. EEG recordings during sleep and wakefulness were obtained. IEA burden was compared before and after PCT. Secondary outcome measures included the sleep spindle rate, the seizure frequency and subjective evaluation in a standardized interview. Results In the cohort of 24 children (10 female, 6.2 ± 3.4 years), IEA burden was lower in the EEG after PCT compared to the baseline (baseline: 5.4% [0.7–97.3] vs. after PCT: 1.5% [0–96.9], p = 0.001, d = −0.41). Sleep physiology expressed by sleep spindles improved after PCT with enhanced fast spindle rates (0.8/min [0–2.2] vs. 1.5/min [0.2–3.4], p = 0.045, d = 0.36). Seizure frequency was decreased in 17 of the 24 patients (70.8%) with one patient achieving seizure freedom. The majority of patients improved in quality of life (79.2%), and sleep (81.3%). No serious adverse effects were documented. Significance This study systematically assessed the effect of PCT in children with genetic / suspected genetic drug‐resistant epilepsy. PCT was found to not only reduce the IEA burden but also increase sleep spindle rates, which are important for cognitive functioning. Plain Language Summary In this study, children with a form of epilepsy, which is resistant against antiseizure medication, received a systematic treatment with corticosteroids over multiple cycles in the hospital. It was found that not only the epileptic activity was reduced but also the sleep of the patients was improved after the treatment. These findings could provide the basis for extending the use of corticosteroids in children with epilepsy

IRF7: activation, regulation, modification and function

Interferon regulatory factor 7 (IRF7) was originally identified in the context of Epstein–Barr virus (EBV) infection, and has since emerged as the crucial regulator of type I interferons (IFNs) against pathogenic infections, which activate IRF7 by triggering signaling cascades from pathogen recognition receptors (PRRs) that recognize pathogenic nucleic acids. Moreover, IRF7 is a multifunctional transcription factor, underscored by the fact that it is associated with EBV latency, in which IRF7 is induced as well as activated by the EBV principal oncoprotein latent membrane protein-1 (LMP1). Aberrant production of type I IFNs is associated with many types of diseases such as cancers and autoimmune disorders. Thus, tight regulation of IRF7 expression and activity is imperative in dictating appropriate type I IFN production for normal IFN-mediated physiological functions. Posttranslational modifications have important roles in regulation of IRF7 activity, exemplified by phosphorylation, which is indicative of its activation. Furthermore, mounting evidence has shed light on the importance of regulatory ubiquitination in activation of IRF7. Albeit these exciting findings have been made in the past decade since its discovery, many questions related to IRF7 remain to be addressed