The autistic phenotype in Down syndrome: differences in adaptive behaviour versus Down syndrome alone and autistic disorder alone

The autistic phenotype in Down syndrome (DS) is marked by a characteristic pattern of stereotypies, anxiety and social withdrawal. Our aim was to study adaptive behaviour in DS with and without autistic comorbidity using the Vineland Adaptive Behaviour Scales(VABS), the Childhood Autism Rating Scales (CARS and the DSM IV-TR criteria. We assessed 24 individuals and established three groups: Down syndrome (DS), DS and autistic disorder(DS-AD), and autistic disorder (AD). The DS and DS-AD groups showed statistically significantly similar strengths on the VABS (in receptive and domestic skills). The DS and DS-AD subjects also showed similar strengths on the CARS (in imitation and relating), differing significantly from the AD group. The profile of adaptive functioning and symptoms in DS-AD seemed to be more similar to that found in DS than to the profile emerging in AD. We suggest that the comorbidity of austistic symptoms in DS hampered the acquisition of adaptive skills more than did the presence of DS alone

The Surplus Effect in Adaptive Behaviour in Down Syndrome: What Can Promote It?

Background: In Down syndrome (DS), adaptive behaviour often shows a “surplus effect” (i.e., higher adaptive abilities than expected from cognitive skills). As inclusive schooling has become mandatory in Italy, we studied the impact of school inclusion on the surplus effect of adaptive behaviour in adult DS, considering potential confounding factors such as parental education. Methods: All consecutive DS individuals from three different sites were queried prospectively regarding type of schooling (inclusive and non-inclusive). Demographic data were documented; cognitive abilities and adaptive behaviour were assessed (Coloured Progressive Matrices and Vineland Adaptive Behaviour Scales). The aim was to establish the presence of a surplus effect in adaptive behaviour, primarily in the overall level and secondarily in the main domains and subdomains. A multivariable-adjusted logistic regression model was used for the association of schooling, and parental education. Results: The majority (65%) showed a surplus effect in adaptive behaviour and had attended inclusive schools (85%). Higher adaptive skills as well as early and longer functional treatment programmes were more readily available for younger individuals. In the group of inclusive schooling, the surplus effect on overall adaptive behaviour was present in 70% as opposed to 38% in the group without inclusive schooling, significant when adjusted for gender and maternal education. This was also observed in socialisation, written, and community, and after adjustment in playing and leisure time. Conclusions: Adaptive behaviour showed a surplus effect in the majority of DS adults, even more so after inclusive schooling. Younger adults showed higher adaptive skills. Moreover, female gender and higher maternal educational level significantly enhanced this surplus effect

Vision problems in Down syndrome adults do not hamper communication, daily living skills and socialisation

Vision problems in Down syndrome adults do not hamper communication, daily living skills and socialisatio

Epilepsy surgery in infants: Safety issues and developmental outcome

Purpose: To evaluate the efficacy and safety of epilepsy surgery in infants. Methods: Included were patients with epilepsy onset during the first year of life, epilepsy surgery before the age of 36 months at the study center and a minimum follow-up of 24 months after surgery. Patients who were surgically treated before the age of 12 months were compared with those between 13 and 36 months. Group differences with respect to efficacy (seizure outcomes and developmental progress measured by the social interaction quotient, SIQ) as well as safety (i. e. peri-operative complication rates) were analyzed. Results: A total of 20 patients (10 girls) were included: 10 (five girls) were operated on as infants (median age at surgery 9.0 months, median disease duration prior to surgery 5.0 months) and 10 (5 girls) were operated on as toddlers (median age at surgery 24.0 months, median disease duration prior to surgery 18.0 months). Favorable seizure outcomes (Wieser 1a and 1) were seen in 80% (8/10) of the infants and 60.0% (6/10) of toddlers. Developmental progress was most evident in infants who were seizure-free and off medication (median SIQ 85.5 versus 63.0 in the toddler group). There were no differences between the two groups with respect to safety aspects. Conclusion: Despite several limitations due to the small number of patients included, our results are in favor of early epilepsy surgery in infants with drug-resistant epilepsy

Efficacy and safety of Everolimus in children with TSC - associated epilepsy – Pilot data from an open single-center prospective study

Abstract Background Epilepsy occurs in up to 90 % of all individuals with tuberous sclerosis complex (TSC). In 67 % disease onset is during childhood. In ≥ 50 % seizures are refractory to currently available treatment options. The mTOR-Inhibitor Everolimus (Votubia®) was approved for the treatment of subependymal giant cell astrocytoma (SEGA) and renal angiomyolipoma (AML) in Europe in 2011. It’s anticonvulsive/antiepileptic properties are promising, but evidence is still limited. Study aim was to evaluate the efficacy and safety of Everolimus in children and adolescents with TSC-associated epilepsies. Methods Inclusion-criteria of this investigator-initiated, single-center, open, prospective study were: 1) the ascertained diagnosis of TSC; 2) age ≤ 18 years; 3) treatment indication for Votubia® according to the European Commission guidelines; 4) drug-resistant TSC-associated epilepsy, 5) prospective continuous follow-up for at least 6 months after treatment initiation and 6) informed consent to participate. Votubia® was orally administered once/day, starting with 4.5 mg/m2 and titrated to achieve blood trough concentrations between 5 and 15 ng/ml. Primary endpoint was the reduction in seizure frequency of ≥ 50 % compared to baseline. Results Fifteen patients (nine male) with a median age of six (range; 1–18) years fulfilled the inclusion criteria. 26 % (4/15) had TSC1, 66 % (10/15) had TSC2 mutations. In one patient no mutation was found. Time of observation after treatment initiation was median 22 (range; 6–50) months. At last observation, 80 % (12/15) of the patients were responders, 58 % of them (7/12) were seizure free. The overall reduction in seizure frequency was 60 % in focal seizures, 80 % in generalized tonic clonic seizures and 87 % in drop attacks. The effect of Everolimus was seen already at low doses, early after treatment initiation. Loss of efficacy over time was not observed. Transient side effects were seen in 93 % (14/15) of the patients. In no case the drug had to be withdrawn. Conclusion Everolimus seems to be an effective treatment option not only for SEGA and AML, but also for TSC-related epilepsies. Although there are potential serious side effects, treatment was tolerated well by the majority of patients, provided that patients are under close surveillance of epileptologists who are familiar with immunosuppressive agents

Ketogenic parenteral nutrition in 17 pediatric patients with epilepsy

Objective Ketogenic parenteral nutrition (kPN) is indicated when enteral intake is temporarily limited or impossible, but evidencebased prescriptions are lacking. Objective was to evaluate the efficacy and safety of kPN in children with epileptic encephalopathies using a new computerbased algorithm for accurate component calculating. Methods Children with epilepsy receiving kPN were included. A computerbased algorithm was established on the basis of guidelines of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN): fat intake not exceeding 4 g/kg/day, ageadequate supply of protein, electrolytes, vitamins, and trace elements, but reduced carbohydrates. Primary outcome was successfully reaching relevant ketosis, defined as betahydroxybutyrate plasma level of 2 mmol/L. Efficacy was defined as seizure reduction 50% in de novo kPN and maintenance of response in children already on a ketogenic diet (KD). Safety was assessed by adverse effects, laboratory findings, and the appropriateness of nutritional intake. Results Seventeen children (median 1.84 years) were studied, of which 76% (13/17) were already on an oral ketogenic diet. Indications for kPN were surgery, status epilepticus, vomiting, food refusal, and introduction of enteral feeding in neonates. The parenteral fat/nonfat ratio was mean 0.9 (0.3; range 0.61.5). Relevant ketosis was reached in 10 children (median 2.9 mmol/L), but not in 7 (median = 1.4 mmol/L). In de novo kPN, significant response was observed in 50% (2/4); in patients previously responding to the KD (77%, 10/13), response was maintained. A significant correlation between the degree of ketosis and seizure reduction (correlation coefficient = 0.691; p = .002) was observed. Only mild and transient adverse events occurred during kPN. Significance KPN with fat intake of 3.54.0 g/kg/day was safe and effective. KPN was tailored according to guidelines and individual nutritional needs. In nearly half of the patients, ketosis was lower than during oral KD. Despite this, seizures remained controlled.(VLID)481548

Ketogenic diet guidelines for infants with refractory epilepsy

Background The ketogenic diet (KD) is an established, effective non-pharmacologic treatment for drug resistant childhood epilepsy. For a long time, the KD was not recommended for use in infancy (under the age of 2 years) because this is such a crucial period in development and the perceived high risk of nutritional inadequacies. Indeed, infants are a vulnerable population with specific nutritional requirements. But current research shows that the KD is highly effective and well tolerated in infants with epilepsy. Seizure freedom is often achieved and maintained in this specific patient group. There is a need for standardised protocols and management recommendations for clinical use. Method In April 2015, a project group of 5 experts was established in order to create a consensus statement regarding the clinical management of the KD in infants. The manuscript was reviewed and amended by a larger group of 10 international experts in the KD field. Consensus was reached with regard to guidance on how the diet should be administered and in whom. Results The resulting recommendations include patient selection, pre-KD counseling and evaluation, specific nutritional requirements, preferred initiation, monitoring of adverse effects at initiation and follow-up, evaluation and KD discontinuation. Conclusion This paper highlights recommendations based on best evidence, combined with expert opinions and gives directions for future research