Real-world data on cannabidiol treatment of various epilepsy subtypes: A retrospective, multicenter study.

OBJECTIVE: Cannabidiol (CBD) is approved for treatment of Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC). Several studies suggest antiseizure effects also beyond these three epilepsy syndromes. METHODS: In a retrospective multicenter study, we analyzed the efficacy and tolerability of CBD in patients with epilepsy at 16 epilepsy centers. RESULTS: The study cohort comprised 311 patients with epilepsy with a median age of 11.3 (0-72) years (235 children and adolescents, 76 adults). Therapy with CBD was off-label in 91.3% of cases due to age, epilepsy subtype, lack of adjunct therapy with clobazam, and/or higher dose applied. CBD titration regimens were slower than recommended, with good tolerability of higher doses particularly in children. Of all patients, 36.9% experienced a reduction in seizure frequency of >50%, independent of their epilepsy subtype or clobazam co-medication. The median observation period was 15.8 months. About one third of all patients discontinued therapy within the observation period due to adverse effects or lack of efficacy. Adverse effects were reported frequently (46.9%). SIGNIFICANCE: Our study highlights that CBD has an antiseizure effect comparable to other antiseizure medications with a positive safety profile independent of the epilepsy subtype. Comedication with clobazam was not associated with a better outcome. Higher doses to achieve seizure frequency reduction were safe, particularly in children. These findings call for further trials for an extended approval of CBD for other epilepsy subtypes and for children <2 years of age.

Differences in Cerebellar Volume as a Diagnostic and Prognostic Biomarker in Children and Adolescents With Epilepsy of Unknown Etiology.

INTRODUCTION AND OBJECTIVE: Epilepsy is one of the most common brain diseases during childhood and adolescence. Atrophy in different brain areas is possible during epilepsy. This study aimed to verify whether cerebellar volume differences could be detected by volume analysis using magnetic resonance imaging (MRI) in children with epilepsy. METHOD: In this retrospective study, 41 children (3.1-18.8 years) with epilepsy of unknown etiology were included (duration of epilepsy 1.9 ± 3 years). A cranial MRI with a volumetric 3-dimensional, T1-weighted sequence was used for volume analysis. The MRIs of 26 patients with headache (5.3-17.1 years) were analyzed for comparison. A volume analysis of the cerebellum was performed using region-based morphometry. Total cerebellar volume, total white and gray matter volume, and 48 regional lobules (L), separated into white and gray matter, were calculated. Cerebellar volumes are presented in relative ratios as the volume fraction of cerebellar volume to total intracranial volume: CV/TIV. RESULTS: The ratio of overall white matter volume was significantly lower in the case group (23.93 × 10-3, P = .039). A significantly lower ratio of regional white matter volume was detected in LV right (P = .031) and left (P = .014), in LVIIIB right (P = .011) and left (P = .019), and in LVIIIA left (P = .009). CONCLUSION: Our results emphasize that volume analysis of the total cerebellar volume alone is insufficient to characterize cerebellar differences in children with epilepsy. Rather, in specific cerebellar region volume analysis using region-based morphometry, children with epilepsy showed significantly lower regional volumes of lobules, which are important for sensorimotor function (LV, LVIII) and higher cognitive function (crus I).

Microcephaly, short stature, and limb abnormality disorder due to novel autosomal biallelic DONSON mutations in two German siblings.

Recently, variants in DONSON have been reported to cause different disorders of the microcephalic primordial dwarfism spectrum. Using whole-exome sequencing, we identified two novel, compound heterozygous DONSON variants in a pair of siblings, one of whom was previously diagnosed with Fanconi anemia. This occurred because the present cases exhibited clinical findings in addition to those of the microcephalic primordial dwarfism disorder, including severe limb malformations. These findings suggest that the DONSON and Fanconi anemia proteins could have supplementary roles in developmental processes as they have in the maintenance of genomic integrity, resulting in related disease phenotypes.

Adiponectin serum concentrations in newborn at delivery appear to be of fetal origin.

OBJECTIVE: Adiponectin (APN) may play a role in adapting energy metabolism at the maternal-fetal unit. The aim of the study was to investigate the relationship between placental APN mRNA expression, maternal serum APN concentration and umbilical cord serum APN concentration in full-term healthy newborns. METHODS: Serum APN levels were compared in 46 samples (23 from healthy newborns; gestational age 37.0 to 41.5 weeks) and their mothers (n=23). The APN concentration was measured using enzyme linked immunosorbent assay (ELISA). We analyzed the mRNA expression profile of APN in 22 placenta tissue samples using real time polymerase chain reaction (RT-PCR). RESULTS: The highest APN serum concentrations were found in umbilical cord blood, these were significantly higher than maternal APN levels (mean concentration±SD; 38.48±12.8 vs. 6.6±2.3 µg/mL, p<0.001). Otherwise, there were no significant correlation between maternal APN and umbilical cord APN concentration. APN gene expression was very low and only found in 8 out of 22 placentas. There were no significant correlation between placental APN mRNA and umbilical cord serum APN or maternal serum APN concentration. Umbilical cord APN concentrations were positively associated with birth weight (r=0.535; p=0.012) and gestational age (r=0.559; p=0.013). Maternal APN concentration revealed a negative correlation between maternal body weight (r=-0.623; p=0.009) and body mass index (BMI) (r=-0.634; p=0.008) at delivery. Additionally, no significant correlation was found between newborn birth weight and maternal weight. CONCLUSIONS: This study suggests that high serum APN concentrations in umbilical cord blood are not regulated by placental APN mRNA gene expression. The high concentration of APN in cord blood is independent from maternal APN concentration, suggesting an important physiological role of APN and implicating that umbilical APN concentration reflects its exclusive production by fetal tissues.