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.

Potential of Dual and Multi Energy XRT and CT Analyses on Iron Formations.

Dual and multi energy X-ray transmission imaging (DE-/ME-XRT) are powerful tools to acquire quantitative material characteristics of diverse samples without destruction. As those X-ray imaging techniques are based on the projection onto the imaging plane, only two-dimensional data can be obtained. To acquire three-dimensional information and a complete examination on topology and spatial trends of materials, computed tomography (CT) can be used. In combination, these methods may offer a robust non-destructive testing technique for research and industrial applications. For example, the iron ore mining and processing industry requires the ratio of economic iron minerals to siliceous waste material for resource and reserve estimations, and for efficient sorting prior to beneficiation, to avoid equipment destruction due to highly abrasive quartz. While XRT provides information concerning the thickness, areal density and mass fraction of iron and the respective background material, CT may deliver size, distribution and orientation of internal structures. Our study shows that the data provided by XRT and CT is reliable and, together with data processing, can be successfully applied for distinguishing iron oxide rich parts from waste. Furthermore, heavy element bearing minerals such as baryte, uraninite, galena and monazite can be detected.

Anti-NMDA receptor encephalitis presenting as atypical anorexia nervosa: an adolescent case report.

Since 2007, more than 600 patients have been diagnosed with anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, with almost 40 % of those affected being children or adolescents. In early phases of the illness, this life-threatening disease is characterized by psychiatric symptoms, such as depression, anxiety, obsessions, hallucinations or delusions. Consequently, a high percentage of patients receive psychiatric diagnoses at first, hindering the crucial early diagnosis and treatment of the anti-NMDA receptor encephalitis. We report on a 15-year-old girl initially presenting with pathological eating behaviour and significant weight loss resulting in an (atypical) anorexia nervosa (AN) diagnosis. Her early course of illness, diagnostic process, treatment and short-term outcome are described. This case report aims to raise awareness about the association between anorectic behaviour and anti-NMDA receptor encephalitis and highlight the importance of multidisciplinary teams in child and adolescent services.

Predictors for the benefit of selective dorsal rhizotomy.

Selective dorsal rhizotomy (SDR) is a spasticity reducing treatment option for children with spastic cerebral palsy. Selection criteria for this procedure are inconclusive to date. Clinical relevance of the achieved functional improvements and side effects like the negative impact on muscle strength are discussed controversially. In this prospective cohort study one and two year results of 54 children with a mean age of 6.9 (±2.9) years at the time of SDR are analyzed with regard to gross motor function and factors affecting the functional benefit. Only ambulatory children who were able to perform a gross motor function measure test (GMFM-88) were included in this study. Additionally, the modified Ashworth scale (MAS), a manual muscle strength test (MFT), and the body mass index (BMI) were evaluated as possible outcome predictors. MAS of hip adductors and hamstrings decreased significantly (p<0.001) and stayed reduced after two years, while GMFM improved significantly from 79% to 84% 12 months after SDR (p<0.001) and another 2% between 12 and 24 months (p=0.002). Muscle strength did improve significantly concerning knee extension (p=0.008) and ankle dorsiflexion (p=0.006). The improvement of function correlated moderately with age at surgery and preoperative GMFM and weakly with the standard deviation score of the BMI, the dorsiflexor and plantarflexor strength preoperatively as well as with the reduction of spasticity of the hamstrings and the preoperative spasticity of the adductors and hamstrings. Correctly indicated SDR reduces spasticity and increases motor skills sustainably in children with spastic cerebral palsy corresponding to clinically relevant changes of GMFM without compromising muscular strength. Outcome correlates to GMFM and age rather than to MAS and maximal strength testing. The data of this evaluation suggest that children who benefit the most from SDR are between 4 and 7 years old and have a preoperative GMFM between 65% and 85%.

Use of intrathecal baclofen in children and adolescents: interdisciplinary consensus table 2013.

In recent years, intrathecal baclofen (ITB) has attained an important role in the treatment of severe spasticity and dystonia in children. There are principal differences between the use of ITB in children and its use in neurology and oncology in adults. Here, we present a consensus report on best practice for the treatment of severe spastic and dystonic movement disorders with ITB. Using a problem-orientated approach to integrate theories and methods, the consensus was developed by an interdisciplinary group of experienced ITB users and experts in the field of movement disorders involving 14 German centers. On the basis of the data pooled from more than 400 patients, the authors have summarized their experience and supporting evidence in tabular form to provide a concise, but still a comprehensive information base that represents our current understanding regarding ITB treatment options in children and adolescents.

Changes in hip geometry after selective dorsal rhizotomy in children with cerebral palsy.

PURPOSE: Hip development in children with spastic cerebral palsy (CP) may be different in comparison to that of typical developing children due to impaired motor function and altered lever arms. Selective dorsal rhizotomy (SDR) is known to reduce spasticity. It is postulated that it also improves mobility. Its influence on hip development is unclear. The aim of this study is to evaluate changes in hip geometry before and after selective dorsal rhizotomy. METHODS: Conventional radiographs (Rippstein I and II) of 33 ambulatory children aged 2.67 to 11.75 years who underwent SDR were analysed pre- and postoperatively at a mean of 18 months (range 12-29 months). Migration percentage, acetabular index, and anteversion were evaluated. The reduction of spasticity was measured with the modified Ashworth scale. A priori power analysis was performed. As data was normally distributed statistical analysis was performed applying the t-test for paired variables. RESULTS: Radiographic parameters concerning hip geometry improved significantly after SDR. The spasticity of adductors and hamstrings was significantly reduced through SDR from on average 1.7 to 0.8 on the modified Ashworth scale (p<0.001). The acetabular index decreased from 19° to 17° (p = 0.001), the migration percentage improved from 24% to 21% (p<0.001). Anteversion was also significantly reduced from 41° to 38° (p<0.001). Function improved significantly from 80% to 85% when measured with the GMFM-88 (p<0.001). CONCLUSIONS: The results confirm that SDR improves hip geometry as well as function in ambulatory CP children. Long-term studies need to show whether this radiographic improvement has clinical relevance with regard to pain and function.

Recurrent stroke due to a novel voltage sensor mutation in Cav2.1 responds to verapamil.

BACKGROUND AND PURPOSE: Familial hemiplegic migraine is characterized by recurrent migraine, hemiparesis, and ataxia. Causes may be mutations in calcium and sodium channels or in a subunit of the Na/K-ATPse. Migraine treatment with calcium channel blockers was only successful in some patients. Summary of Case- We describe a 6-year-old girl with recurrent ischemic strokes after minor head trauma associated with seizures, hemiparesis, fever, and altered consciousness. Genetic analysis revealed a spontaneous, novel dominant CACNA1A mutation (c.4046G→A, p.R1349Q) that removed a highly conserved arginine of the voltage sensing region of the P/Q-type Ca(v)2.1 channel. Because a homologous mutation in the tottering-5J mouse increased open probability of the channel as well as calcium influx, we treated the patient with the calcium channel blocker verapamil during characteristic prodromi after head trauma. Treatment was instantly effective and prevented a new stroke. CONCLUSIONS: CACNA1A mutations should be considered in the diagnostic workup of childhood stroke, especially if associated with ataxia and migraine.

DNA repair capacity in lymphocytes of nasopharyngeal cancer patients.

Possible hereditary factors in the tumorigenesis of nasopharyngeal cancer (NPC) have not yet been clearly identified. In the present study, the DNA repair capacity of lymphocytes after exposure to the nitrosamine NDEA was quantified in order to elucidate whether this measure may be a factor in susceptibility to NPC. The alkaline single-cell microgel electrophoresis (Comet) assay was used to quantify chemically induced DNA damage and repair capacity in lymphocytes of 30 NPC patients (NPC) and 29 non-tumor donors (NTD). The induction of DNA single strand breaks, alkali labile and incomplete excision repair sites after exposure of lymphocytes to NDEA was assessed as differences between repair intervals of 0 min, 15 min, 30 min and 60 min, respectively. A RC(total) was assessed using the difference between the OTMs of 0 min of repair time and the 60-min repair interval for both groups. Repair capacities (RC) were calculated for the intervals according to the Olive Tail Moment (OTM), a quantitative measure for DNA migration in the Comet assay for the group of NPC patients and the NTD, accordingly. RCs were compared between the two groups using the Mann-Whitney U-Test. RC(15 min), RC(30 min) RC(60 min) and the RC(total) after a 60-min repair interval demonstrated no significant difference between the two groups. Furthermore, when comparing grades of DNA migration (OTM<2, 2-5, 5-10, 10-20, 20-30 and >30), there were no differences evident. In this investigation, rejoining of DNA single strand breaks in lymphocytes of NPC and NTD appeared to be accomplished to an equal degree and in equal time periods. However, the applied method does not give evidence concerning the quality of the single strand break rejoining processes. In this group of patients, tumorigenesis in NPC could not be associated with a decreased DNA repair capacity.