Valproate-associated reversible encephalopathy in a 3-year-old girl with Pallister-Killian syndrome

Valproic acid (VPA) is considered to be a drug of first choice for the therapy of generalized and focal epilepsies, including special epileptic syndromes. The drug is usually well tolerated, rare serious complications may occur in some patients, including hemorrhagic pancreatitis, coagulapathies, bone marrow suppression, VPA-induced hepatotoxicity and encephalopathy. We report a case of VPA-associated encephalopathy without hyperammonemia in a 3-year-old girl with Pallister-Killian-Syndrom, combined with a mild hepatopathy and thrombopathy. After withdrawal of VPA, the clinical symptoms and the electroencephalography-alterations vanished rapidly

Capillary microscopy and hemorheology in children during antiepileptic monotherapy with carbamazepine and valproate

SummaryThe interactions of epilepsy and antiepileptic therapy an one hand and cardiovascular system on the other hand are multiple and complex. Antiepileptic drugs (AEDs) cause alterations of serum lipids and of the fatty acid composition of the membranes. Homocystein, known to induce vascular endothelial damage was found to be elevated in patients on valproate (VPA) and carbamazepine (CBZ) therapy. Marked coronary artherosclerosis and myocardial infarction may already occur in children treated with CBZ. Community based studies corroborated a higher incidence of myocardial infarction, peripheral vascular diseases hypercholesterinemia, left ventricle hypertrophy and stroke in patients with epilepsy. In this context, we wanted to elevate changes of microcirculation related to AEDs commonly prescribed such as VPA and CBZ.Capillary microscopy is a non-invasive technique for measuring the velocity of red blood cells and for determining nutritional blood flow in the capillaries of the skin. It can easily be performed in children.The aim of this study was to look for possible effects an antiepileptic monotherapy with carbamazepine or valproate has on the peripheral microcirculation in epileptic children.We were able to examine 14 children with CBZ and 24 children with VPA, recruited in our neuropediatric Unit. The results were compared to normative values, determined in former analyses of 207 healthy children. We found significant differences in capillary density, tortuous index of the capillaries, capillary diameter and flow rate of erythrocytes for both antiepileptic drugs. Additionally, there were changes in plasma viscosity and the aggregation of erythrocytes.These microcapillary effects could be of special interest in the relationship of a long-term antiepileptic therapy and the development of vascular diseases.We suggest that the influence of AEDs on microcirculation should also be considered in further studies on cardiovascular changes in patients with antiepileptic long-term medication

Problematic Internet Use among Adolescents 18 Months after the Onset of the COVID-19 Pandemic

Studies in recent years and especially since the beginning of the COVID-19 pandemic have shown a significant increase in the problematic use of computer games and social media. Adolescents having difficulties in regulating their unpleasant emotions are especially prone to Problematic Internet Use (PIU), which is why emotion dysregulation has been considered a risk factor for PIU. The aim of the present study was to assess problematic internet use (PIU) in adolescents after the third wave (nearly 1.5 years after the onset in Europe) of the COVID-19 pandemic. In the German region of Siegen-Wittgenstein, all students 12 years and older from secondary-level schools, vocational schools and universities were offered a prioritized vaccination in August 2021 with an approved vaccine against COVID-19. In this context, the participants filled out the Short Compulsive Internet Use Scale (SCIUS) and two additional items to capture a possible change in digital media usage time and regulation of negative affect due to the COVID-19 pandemic. A multiple regression analysis was performed to identify predictors of PIU. The original sample consisted of 1477 participants, and after excluding invalid cases the final sample size amounted to 1268 adolescents aged 12–17 (x = 14.37 years, SD = 1.64). The average prevalence of PIU was 43.69%. Gender, age, digital media usage time and the intensity of negative emotions during the COVID-19 pandemic were all found to be significant predictors of PIU: female gender, increasing age, longer digital media usage time and higher intensity of negative emotions during the COVID-19 pandemic were associated with higher SCIUS total scores. This study found a very high prevalence of PIU among 12- to 17-year-olds for the period after the third wave of the COVID-19 pandemic, which has increased significantly compared to pre-pandemic prevalence rates. PIU is emerging as a serious problem among young people in the pandemic. Besides gender and age, pandemic-associated time of digital media use and emotion regulation have an impact on PIU, which provides starting points for preventive interventions

De novo missense variants in FBXO11 alter its protein expression and subcellular localization.

Recently, we and others identified de novo FBXO11 variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. The mutational spectrum includes intragenic deletions, likely gene disrupting and missense variants distributed across the protein. To further characterize the functional consequences of FBXO11 missense variants, we analyzed their effects on protein expression and localization by overexpression of 17 different mutant constructs in HEK293 and HeLa cells. We found that the majority of missense variants resulted in subcellular mislocalization and/or reduced FBXO11 protein expression levels. For instance, variants located in the nuclear localization signal and the N-terminal F-Box domain lead to altered subcellular localization with exclusion from the nucleus or the formation of cytoplasmic aggregates and to reduced protein levels in western blot. In contrast, variants localized in the C-terminal Zn-finger UBR domain lead to an accumulation in the cytoplasm without alteration of protein levels. Together with the mutational data our functional results suggest that most missense variants likely lead to a loss of the original FBXO11 function and thereby highlight haploinsufficiency as the most likely disease mechanism for FBXO11-associated NDDs

De novo missense variants in FBXO11 alter its protein expression and subcellular localization.

Recently, we and others identified de novo FBXO11 variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. The mutational spectrum includes intragenic deletions, likely gene disrupting and missense variants distributed across the protein. To further characterize the functional consequences of FBXO11 missense variants, we analyzed their effects on protein expression and localization by overexpression of 17 different mutant constructs in HEK293 and HeLa cells. We found that the majority of missense variants resulted in subcellular mislocalization and/or reduced FBXO11 protein expression levels. For instance, variants located in the nuclear localization signal and the N-terminal F-Box domain lead to altered subcellular localization with exclusion from the nucleus or the formation of cytoplasmic aggregates and to reduced protein levels in western blot. In contrast, variants localized in the C-terminal Zn-finger UBR domain lead to an accumulation in the cytoplasm without alteration of protein levels. Together with the mutational data our functional results suggest that most missense variants likely lead to a loss of the original FBXO11 function and thereby highlight haploinsufficiency as the most likely disease mechanism for FBXO11-associated NDDs

Rating e-Tailer's Money-Back Guarantees

Most e-tailers offer money-back guarantees (MBGs) on product returns, but coverage and durations of different policies vary significantly across e-tailers (taking into account restocking fees, shipping and handling fees, and coverage duration). To help consumers and e-tailers evaluate MBG policies, we developed three different MBGQual (money-back guarantee quality) indexes that measure the insurance protection, costs, and attractiveness of the MBGs to consumers. The usefulness of these indexes is illustrated by examining MBGs offered by electronic product e-tailers

A Survey on Cannabinoid Treatment of Pediatric Epilepsy Among Neuropediatricians in Scandinavia and Germany

Objectives: There is an increasing interest in cannabinoid-based products for the treatment of refractory pediatric epilepsy. However, a licensed cannabidiol (CBD) product was first approved for use by the European regulatory authorities in 2019. We aimed to obtain knowledge about clinical experience and attitudes toward cannabinoid use for epilepsy treatment among neuropediatricians in Scandinavia and Germany in the era before a CBD-product was commercially licensed and available. Study design: An internet-based questionnaire (Survey Monkey) was distributed by email to members of neuropediatric societies in Sweden, Germany, Denmark, and Norway between February and April 2018. One reminder email was sent. Results: Eighty-six responded. Only 10 of 86 (12%) respondents had personal experience with off-label prescription of cannabinoid-based products, mainly for severe refractory pediatric epilepsies like Dravet syndrome and Lennox-Gastaut syndrome. However, 49 respondents (57%) had been exposed to relatives of patients that had requested or wanted to discuss cannabinoid therapy, and 32 (37%) respondents knew about cannabinoid self-medication. The knowledge regarding cannabinoid-based therapy among the respondents was overall limited. Main reasons for not prescribing cannabinoid-based therapy were concerns about law regulations and lack of an available product. Conclusion: Off-label cannabinoid-based therapy for pediatric epilepsy was not widely prescribed by neuropediatricians in Scandinavia and Germany in 2018