Anastasia Dressler

Epilepsy surgery in children and adolescents with malformations of cortical development—-Outcome and impact of the new ILAE classification on focal cortical dysplasia

UNLABELLED To determine long-term efficacy and safety of epilepsy surgery in children and adolescents with malformations of cortical development (MCD) and to identify differences in seizure outcome of the various MCD subgroups. Special focus was set on the newly introduced International League Against Epilepsy (ILAE) classification of focal cortical dysplasia (FCD). STUDY DESIGN This is a single center retrospective cross-sectional analysis of prospectively collected data. INCLUSION CRITERIA age at surgery <18 years, pre-surgical evaluation and epilepsy surgery performed at the Vienna pediatric epilepsy center, histologically proven MCD, complete follow-up data for at least 12 months. Clinical variables evaluated: type and localization of MCD, type of surgery and a variety of clinical characteristics reported to be associated with (un-)favorable outcomes. MCD were classified following the existing classification schemes (Barkovich et al., 2012. Brain. 135, 1348-1369; Palmini et al., 2004. Neurology. 62, S2-S8) and the ILAE classification for FCD recently proposed by Blümcke in 2011. Seizure outcome was classified using the ILAE classification proposed by Wieser in 2001. RESULTS 60 Patients (51.7% male) were included. Follow up was up to 14 (mean 4.4 ± 3.2) years. Mean age at surgery was 8.0 ± 6.0 (median 6.0) years; mean age at epilepsy onset was 2.9 ± 3.2 (median 2.0) years; duration of epilepsy before surgery was 4.8 ± 4.4 (median 3.0) years. 80% of the patients were seizure free at last follow-up. AEDs were successfully withdrawn in 56.7% of all patients. Extended surgery, lesion localization in the temporal lobes and absence of inter-ictal spikes in postsurgical EEG recordings were predictive of favorable seizure outcomes after surgery. However, no association was found between outcome and MCD sub-types. Epilepsy surgery is highly effective in carefully selected drug-resistant children with MCD. Surrogate markers for complete resection of the epileptogenic zone remain the only significant predictors for seizure freedom after surgery.

Vertical perithalamic hemispherotomy: A single‐center experience in 40 pediatric patients with epilepsy

The current concept for hemispherotomy includes various lateral techniques and the vertical perithalamic hemispherotomy introduced by Delalande in 1992. We have chosen the vertical approach because of advantages that possibly influence outcome: the possibility to completely disconnect the hemisphere at the level of the thalamus obviating both the need to resect the insula and the need to open and dissect the subarachnoid space of the Sylvian fissure.

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.

Adaptive behaviour in Down syndrome: a cross-sectional study from childhood to adulthood

ZusammenfassungEINLEITUNG: In der Literatur werden adaptive Fähigkeiten bei Personen mit Down-Syndrom so beschrieben, dass sie kontinuierlich bis ins Jugendlichenalter wachsen, danach eine Phase der Stagnation beginnt, ein Abfall erst im mittleren Erwachsenenalter eintritt und einer früh beginnenden Demenz vom Alzheimertyp zugeschrieben wird. Der Zeitpunkt der Stagnation der adaptiven und auch der kognitiven Fähigkeiten wird kontrovers diskutiert. Unser Ziel war es das adaptive Verhalten bei Down-Syndrom, die Unterschiede in verschiedenen Altersgruppen, altersabhängige Veränderungen und den Zusammenhang mit den kognitiven Fähigkeiten zu untersuchen. METHODEN: In einer prospektiven Querschnittsstudie wurden alle Personen mit Down-Syndrom an vier verschiedenen italienischen Zentren eingeschlossen. Einschlusskriterien waren, dass die Teilnehmer in der Familie lebten und eine Demenz vom Alzheimertyp ausgeschlossen werden konnte. Die Untersuchungen umfassten eine detaillierte medizinische und neuropsychiatrische Untersuchung, eine psychometrische Testung und die Untersuchung des adaptiven Verhaltens mittels der Vineland Adaptive Behaviour Scales. ERGEBNISSE: 75 Personen von 4 bis 52 Jahren wurden eingeschlossen. Die Gruppe der jungen Erwachsenen zwischen 20 und 30 Jahren zeigte die höchsten adaptiven Fähigkeiten. Der Bereich Kommunikation, durchgehend eine Stärke, zeigte keine Altersunterschiede, die Bereiche Alltagsfertigkeiten ( p = 0,012) und Sozialisierung (p = 0,021) waren im Kindes- und vorallem im mittleren Durchschnitt, während diese hingegen im jüngeren und älteren Erwachsenenalter Stärken darstellten. SCHLUSSFOLGERUNGEN: Personen mit Down-Syndrom stärken ihre adaptiven Fähigkeiten bis zum 30. Lebensjahr, die kognitiven Fähigkeiten haben zu diesem Zeitpunkt schon ein Plateau erreicht. Wir fanden ein größeres Absinken der adaptiven Fähigkeiten im mittleren Erwachsenenalter. Dieses Resultat führen wir zum Teil auf vermehrte Stimuli im Alltag der jüngeren Teilnehmer zurück, was in weiterführenden Studien untersucht werden sollte.SummaryOBJECTIVE: Adaptive behaviour in Down syndrome is described to increase until middle childhood and to begin to decline in adolescence, whereas significant deterioration in middle adulthood has been attributed to early onset of dementia. Nevertheless, opinions diverge about when the slowing down of adaptive and cognitive abilities starts. Our aims were to describe the profile of adaptive behaviour in Down syndrome, the variability within different age- groups, age-related changes and the correlation to cognitive abilities. METHODS: In a prospective cross-sectional study, individuals with Down syndrome all living in the family and without signs of dementia in 4 Italian sites were included and performed a detailed medical and neuropsychiatric work-up, as well as cognitive testing and adaptive behaviour, using the Vineland Adaptive Behaviour Scales. RESULTS: Seventy-five individuals with Down syndrome from 4 to 52 years were included. Adults from 20 to 30 years showed the highest performance of all groups. The area of communication, always an area of strength, did not change over time, in childhood and especially in adolescence daily living skills (p = 0.012) and socialisation (p = 0.021) scored on average, whereas in young and middle adulthood performance in daily living skills and socialisation and were areas of strength. CONCLUSIONS: Individuals with DS continue to increase competence in adaptive behaviour until 30 years, even when cognitive abilities reach a plateau. We found no major decline in middle adulthood. This may be due to exposure to daily life, but needs to be supported by further studies.

Tuberous Sclerosis Complex: new criteria for diagnostic work-up and management

SummaryTuberous sclerosis complex (TSC) is a rare genetic multisystem disorder, characterized by predominantly benign tumors in potentially all organ systems. System involvement, severity of clinical symptoms and the response to treatment are age-dependent and heterogeneous. Consequently, the disorder is still not recognized in a considerable number of patients. The diagnostic criteria and the guidelines for surveillance and management of patients with TSC were revised, and the establishment of specialized TSC-centers was strongly recommended during an International Consensus Conference in 2012. TOSCA (TuberOus SClerosis registry to increase disease Awareness), an international patient registry, was started to allow new insights into the causes of different courses. Finally, there are—since the approval of the mTOR inhibitor Everolimus—promising new therapeutic approaches.This review focuses on the various TSC related symptoms occurring at different ages, the novel recommendations for diagnosis and treatment as well as the need for multidisciplinary follow-up.ZusammenfassungDie Tuberöse Sklerose (TS) ist eine seltene, genetisch bedingte Multisystemerkrankung, die zu (vorwiegend) benignen Tumoren in nahezu allen Organsystemen führen kann. Sowohl Ausprägung und Schweregrad der klinischen Symptome als auch das Ansprechen auf therapeutische Interventionen sind altersabhängig und zudem individuell äußerst heterogen. Es wird daher angenommen, dass viele Betroffene spät oder gar nicht erkannt werden.2012 wurden im Rahmen einer internationalen Konsensus Konferenz die diagnostischen Kriterien, sowie die Richtlinien für Therapie und Überwachung überarbeitet und die Etablierung spezialisierter multidisziplinärer TS-Zentren dringend empfohlen. Mit TOSCA (TuberOus SClerosis registry to increase disease Awareness) wurde zudem ein internationales Patienten-Register geschaffen, das neue Erkenntnisse über die Ursachen unterschiedlicher Ausprägung und Verläufe der Erkrankung ermöglichen soll. Seit der Zulassung des mTOR-Inhibitors Everolimus 2011 ist nun erstmals eine spezifische Multisystem-Therapie verfügbar. Der folgende Review Artikel gibt einen umfassenden Überblick über die verschiedenen Symptome und präsentiert die rezenten Neuerungen bezüglich Diagnostik, Therapie und Verlaufsbeobachtung.

The ketogenic diet in infants – Advantages of early use

OBJECTIVE To evaluate the efficacy and safety of the ketogenic diet (KD) in infants (< 1.5 years of age) compared with older children. METHODS Patients with complete follow-up data of ≥ 3 months after initiation of the KD were analyzed retrospectively. Infants < 1.5 years at initiation of the KD (Group A) were compared with children > 1.5 years (Group B). RESULTS 127 children were screened, 115 (Group A: 58/Group B: 57) were included. There were no significant differences between groups with respect to responder rates (63.8% vs. 57.9% at 3 months), but more infants became seizure free (34.5% vs. 19% at 3 months; 32.7% vs. 17.5% at 6 and 12 months). This result remained stable also after termination of the KD (30.6% vs. 3.9% at last follow-up) (p = 0.000). Looking at infants < 9 months of age separately (n = 42), this result was even stronger with significantly more infants being seizure free at 6 and at 12 months (p = 0.005, p = 0.014, respectively). In addition, a significantly higher number of infants remained seizure free in the long-term (p = 0.001). No group differences between infants and children with respect to safety were observed. Overall 52/115 patients (45.21%) reported side effects, but withdrawal of the KD was only necessary in one infant. Acceptance of the KD was better in infants compared with children at 3 months (0 vs. 14, p = 0.000), but became difficult when solid food was introduced (16 vs. 14; n.s.). SIGNIFICANCE According to our results, the KD is highly effective and well tolerated in infants with epilepsy. Seizure freedom is more often achieved and maintained in infants. Acceptance of the diet is better before the introduction of solid food. Therefore, we recommend the early use of the KD during the course of epilepsy.

Type 1 diabetes and epilepsy: Efficacy and safety of the ketogenic diet

Diabetes type 1 seems to be more prevalent in epilepsy, and low‐carbohydrate diets improve glycemic control in diabetes type 2, but data on the use of the classic ketogenic diet (KD) in epilepsy and diabetes are scarce. We present 15 months of follow‐up of a 3 years and 6 months old girl with diabetes type 1 (on the KD), right‐sided hemiparesis, and focal epilepsy due to a malformation of cortical development. Although epileptiform activity on electroencephalography (EEG) persisted (especially during sleep), clinically overt seizures have not been reported since the KD. An improved activity level and significant developmental achievements were noticed. Glycosylated hemoglobin (HbA1c) levels improved, and glycemic control was excellent, without severe side effects. Our experience indicates that diabetes does not preclude the use of the KD.

Improvement of language development after successful hemispherotomy

PURPOSE To investigate language development after functional hemispherotomy and to evaluate prognostic factors for (un-)favourable outcomes. METHODS Children and adolescents who had vertical perithalamic hemispherotomy at the Medical University Wien (MUW) paediatric epilepsy centre were identified from a prospectively maintained database. Inclusion criteria were: complete clinical, neurophysiological and neuropsychological data, seizure freedom and a minimum follow-up of 12 months after surgery. The language quotients (LQ) prior to surgery and at last follow-up were calculated for each child. In addition, associations between pre- to post-surgical changes in LQ and the following variables were examined: age at epilepsy-onset, age at surgery and duration of epilepsy prior to surgery, aetiology, side of surgery, interictal EEG including sleep organization before and 12 months after surgery and antiepileptic-drug (AED) withdrawal state at last follow-up. Analyses were carried out in SPSS version 20.0 (SPSS Inc., Chicago, IL, USA). Nonparametric Wilcoxon and chi-square tests were applied, as required. RESULTS Data from 28 children (14 female) were analyzed. The median age at epilepsy surgery was 64.5 months. The median follow-up after surgery was 3.0 years (±2.6 years, range 12 months to 12 years). Significant gains in LQs at last follow-up were found in 31% of the children (p=0.008). Short disease duration prior to surgery, acquired pathology, lack of epileptiform EEG discharges in the contralateral hemisphere and/or normalization of EEG sleep patterns after surgery, and successful AED withdrawal were linked to favourable language outcomes. CONCLUSION Successful and early hemispherotomy results in improvement of language function in the intact hemisphere.

Immediate termination of electrical status epilepticus in sleep after hemispherotomy is associated with significant progress in language development.

To study the effect of hemispherotomy on electrical status epilepticus in sleep (ESES) and language development.

Rapporti tra abilità linguistiche, cognitive e profili di sviluppo adattivo in giovani adulti con Sindrome di Down

Stefania Bargagna (IRCSS Stella Maris e Università di Pisa) Valentina Perelli (IRCSS Stella Maris e Università di Pisa) Anastasia Dressler (IRCSS Stella Maris e Università di Pisa) Manuela Pinsuti (IRCSS Stella Maris e Università di Pisa) Alda Colleoni (AUSL Città di Forlì e Centro Regionale per le Disabilità linguistiche e Cognitive in Età Evolutiva AUSL Città di Bologna) Guja Astrea (IRCSS Stella Maris e Università di Pisa) Valentina Rafanelli (IRCSS Stella Maris e Università di Pisa) Anna Maria Chilosi (IRCSS Stella Maris e Università di Pisa)