Lecture 1- Epilepsy and psychiatry in children and adolescents: a Scandinavian perspective

by Christopher Gillberg

Overview:
Several Scandinavian hospital-based centres have services devoted to comprehensive care for children with severe epilepsies, including some where the behavioural and academic problems are taken into account. However, there is a lack of a general plan for integration of services, and child psychiatry/child and adolescent mental health is often not involved at all in the provision of help to families. Outreach and communitybased services are poorly integrated. Progress in the field has been very slow, particularly seen in the perspective of the often devastating effects of epilepsy and in comparison with the steady progress of service development in neighbouring fields, such as autism.

Lecture 2-ASD and epilepsy: new perspectives

by Magnus Landgren

Overview:
For decades it has been well established that epilepsy and EEG pathology are common in ASD. These links point towards a possible common cause in some cases and a reciprocal interplay between epilepsy and ASD in others. It is also now established that cognitive impairment is associated with childhood epilepsy in general, and, in some epileptic encephalopathies, with ASD in particular. ASD, in turn, is comorbid with many other problems, including neuromuscular disorders, disruptive behaviours (including ADHD), intellectual disability, gastrointestinal symptoms, and sleep disorders, to mention but a few.

Based on this knowledge about ESSENCE, children who are undergoing medical investigation because of epilepsy, ASD, ADHD or other neurodevelopmental disorders/ESSENCE, should be examined, followed and receive intervention/treatment in the context of a neurodevelopmental health care team involving close collaboration between paediatricians, child psychiatrists and neurologitsts, and clinical psychologists with neuropsychological training. Each child´s brain is a complex organ and so is its symptomatic expression. This fact should no longer be allowed to be ignored by artificial specialist and administrative boundaries.

The prevalence of ASD, epilepsies, and EEG abnormalities will be presented from a population based local habilitation centre in West Sweden (with 1080 patients). A couple of cases of children with ASD and comorbid epilepsy will also be reviewed.

The following specific questions will be asked (and hopefully adequately answered): When should an EEG be performed in the work-up of children with ASD? What is the role of antiepileptic drug treatment in ASD? What is the role of ‘cognitive mapping’ in childhood epilepsy and ASD?

Lecture 3-Are there any typical cognitive phenotypes in epilepsy

by Colin Reilly 

Overview:
Children with epilepsy are at very significant risk for global and specific deficits in cognitive functioning which can have a very significant negative effect on long-term outcomes. Although the prevalence of cognitive problems in childhood epilepsy has been described in a number of studies there is a lack of population based data on cognitive profiles in childhood epilepsy. Previous studies of cognition in childhood epilepsy are reviewed with a particular emphasis on population based studies and cognitive profiles in childhood epilepsy. Aspects of the Children with Epilepsy in Sussex Schools (CHESS) study, a recent population based study carried out in the UK focusing on cognition and behaviour in children with epilepsy are described. The study employed an epidemiological approach to recruit school aged children (4-16 years) with ‘active’ epilepsy (on AEDs and/or seizure in the last year) in 2011 and 2012. Participants (n=85) in the study were initially screened for academic, behavioural and school attendance problems based on parent and teacher reports. All participants then underwent cognitive assessments and screening for neurodevelopmental disorders. Measures of cognition included the Wechsler Abbreviated Scale of Intelligence (WASI), subtests from the Working Memory Test Battery
for Children (WMTB-C) and Processing Speed Index of the Wechsler Intelligence Scale for Children (WISC-IV). 40% of the children with epilepsy were found to be functioning in the intellectually disabled range of cognitive functioning (IQ<70). With regard to cognitive profile, significantly weaker performance was found on measures of processing speed and working memory compared with verbal and performance IQ. The coding subtest was a significant area of weakness. More than half of participants scored 1SD below their assessed IQ on at least one of the four administered memory tests suggesting specific memory impairments are common in this population. The results of statistical analysis focusing on possible clinical correlates of cognitive impairment in childhood epilepsy including age of onset of epilepsy, duration of epilepsy and AED usage will be discussed. The results will also be discussed with respect to previous studies and implications regarding supporting the children in school and possible interventions to improve cognitive functioning.

Lecture 4-Prenatal exposure to antiepileptic drugs: neurodevelopmental outcomes

by Rebecca Bromley

Overview:
Historically the primary outcomes of research investigating infant outcomes following prenatal exposure to antiepileptic drugs has been the prevalence of major congenital malformations. More recently it has become apparent that it is important to also investigate the neurodevelopmental outcome of infants prenatally exposed to antiepileptic drugs. Recently published evidence from the NEAD study group demonstrates that children prenatally exposed to sodium valproate are at an increased risk of poorer IQ, language, memory and executive functioning at 6 years of age in comparison to children exposed to other antiepileptic drugs. Such findings are consistent with that of other prospective studies in younger children. This talk will review the evidence to date pertaining to neurodevelopmental outcomes following prenatal exposure to antiepileptic drugs.

Lecture 5-New medication for ASD, ADHD and Fragile X Syndrome

by Randi Hagerman 

Overview:
The development of new treatments for neurodevelopmental disorders have depended on advances in molecular biology and the development of animal models so that new treatments can be tested on animals and then tried in patients. Fragile X Syndrome (FXS) has led the way for targeted treatments that can reverse the neurobiological abnormalities and improve behaviour including ADHD symptoms and socialisation in addition to cognitive abilities in animal models. Initial trials have shown promise in children and
adults with FXS and with autism. The use of mGluR5 antagonists, GABA A and B agonists, minocycline and lovastatin will be reviewed. The use of biomarkers including MMP9 activity and mTOR downstream proteins are potential biomarkers for targeted treatments to judge improvement in CNS function in addition to event related potentials (ERPs). Treatments in early childhood appear to have the best results and the targeted treatments should be combined with enhanced learning programs, such as iPAD apps, CogMed, Early Start Denver Model and other intensive programs.

Lecture 6-A new framework for the management of children with epilepsy

by Brian Neville

Overview:
1. Should a frame work for epilepsy management be purely for epilepsy or
neurodevelopmental problems more generally? Ideally these should be
shared at some level.

2. Bangladesh has:
• developmental therapy
• clinical psychology
• paediatricians trained in neurology
• paediatric neurologist
• office manager.
14 University centres now participate and will become generalised to
the whole of Bangladesh if approved.
Use 10 questions as a survey + SDQ e.g. 30% attend approximately
and needs a wider and closer spread.

3. Can Bangladesh lead the way to other countries with limited resources
and with greater attention to community based rehabilitation?
• distance to centre 3-4 miles
• monthly at least
• manage AEDs/cognition/ADHD/ASD/depression
• cheap
• interactive education.
Urgent treatment for status epilepticus (at high and low risk).

4. Western countries:
• UK – adult system
• a great deal of epilepsy is managed by non-neurologists
• non-neurologists may cope with more than AEDs e.g. cognition etc
• must bring together psychiatry, psychology and neurology with
joint budgets, which some groups are doing
• all with active epilepsy must be screened and provided for
from school age
• use of ESSENCE for under 5’s to help with those most
severely affected
• children’s contact should be with all who have epilepsy, i.e. mild
to severe, probably through a mixed referral system. Our major
problem is the provision of comprehensive care.

5. The specialist cases that require detailed investigations and sometimes
surgery are still in their early stages but have four units for England
and specialities within these are moving on. Greater need for surgical
research and urgent need for status epilepticus treatment.

6. Sweden. More comprehensive range of skills but still places where
care it is not comprehensive. Finland, Denmark and Norway I think
follow specialists with neuropsychology access but is not the
case elsewhere.

7. Mental Capacity Assessment Protocol.
This needs to be fed into the individual components of mental capacity.

8. Transition to ‘Adult’.
This goes with mental capacity but we should be working hard to
ensure a smooth passage to whatever stage of adulthood is possible
and avoid the mishaps that might occur e.g. burns.

9. We have therefore a condition in which loss of consciousness and/
or loss of control separates these from other conditions. One wants
to improve children’s appreciation by helping them to have fun, more
serious times and constructing an adolescence for the child/adult
which gives them every possibility of fulfilment but avoiding where
possible obvious hazards, such as burns.

Lecture 7-Acute immunology, temporal lobe epilepsy and other disorders

by Ming Lim

Overview:
Childhood central nervous system (CNS) autoimmune (adaptive immunity) and auto-inflammatory (innate immunity) diseases comprise a large group of immune-mediated encephalitis. Antibodies against the N-methyl-Daspartate receptor (NMDAR) are now recognised in children who develop a sub acute onset encephalopathy, commonly associated with prominent neuropsychiatric symptoms and a florid movement disorder. Less commonly, antibodies to voltage gated potassium channels (VGKC) and its associated proteins are associated with limbic encephalitis, presenting with seizures, amnesia and temporal lobe inflammation. Antibody negative cases are also beginning to be recognised on the basis of similar clinical features. These conditions are often managed with aggressive and usually prolonged immunosuppression, frequently with a beneficial effect.

The expansion of the VGKC-antibody associated phenotype to patients with drug-resistant epilepsy syndromes are beginning to be recognised, as are the reports of antibodies against an increasing range of CNS auto antigens like GAD, Glycine receptor, GABA (B) receptor, AMPA receptor in various epilepsy syndromes; although here the precise pathogenic role of the autoantibodies remain unclear. Moreover, a significant number of these patients are refractory to immunotherapy.

Collectively, the longer term impact on the cognitive and
neurodevelopmental outcome of these children are profound, even in thetreatment responsive group. Although neuroinflammation is implicated, a range of genetic and environmental factors, and their complex interactions within each individual are likely to contribute/mediate this.

Lecture 8-Pathological Demand Avoidance Syndrome (PDA): new findings

by Francesca Happé

Overview:
Pathological Demand Avoidance (PDA) is a term coined to describe children (many with an autism spectrum diagnosis) who show a range of extreme behaviours in response to everyday demands, including social distraction, retreat into role-play, verbal or physical attack. Such children are said to dislike praise, and fail to respond to educational approaches useful for ASD, such as routine and repetition.
Despite normal IQ, children receiving the PDA label often fail in mainstream schools, and the outcome for such young people appears to be poor. To date there has been no systematic research on this possible syndrome or subgroup, despite a substantial UK based web presence. I will discuss some theoretical perspectives on the possible relationship between PDA and Autism Spectrum Disorders, and present some preliminary findings from our on-going research attempting to measure demand avoidance and compare profiles across different clinical groups.

Lecture 9-Debate: Epilepsy surgery - evidence for gains in skills

by Helen Cross

Overview:
Epilepsy surgery is now an accepted treatment in selected children with drug resistant focal epilepsy. The presumed ongoing adverse effect of epileptic seizures on neurodevelopment has been put forward as one reason why epilepsy surgery should be considered early in management, especially in the very young. Determining evidence base for improved outcomes has been challenging.

Early onset epilepsy is associated with poor long-term neurodevelopmental outcome. Prospective evaluation of the benefits of surgery on cognition however remains difficult in view of the duration of follow-up required, and the lack of standardised tests across the age groups. Group studies have demonstrated little change in IQ pre and post operatively. This could be considered as benefit as the developmental trajectory has been maintained rather than slowed, the latter seen in many children with epilepsy. Studies are beginning to demonstrate gains may be achieved following early surgery in a proportion, e.g. those with a history of epileptic spasms where epileptic encephalopathy may be contributory to the cognitive impairment. This will not however be seen in all. A more recent study of young adults who underwent temporal lobe resection in childhood has demonstrated maintained IQ for the first 6 years following surgery, with subsequent gains highly related to wean of medication. There may therefore be in fact two possibilities following surgery for drug resistant epilepsy: immediate effect should there be evidence of an epileptic encephalopathy, or longer term benefit attributable to drug wean and possibly reorganisation of networks.

Lecture 10-Debate: Epilepsy surgery - evidence for lack of gains in skill

by Paul Uvebrant

Overview:
The development in 17 children of cognitive functions and the sustainability of seizure control between two and ten years after epilepsy surgery were prospectively investigated. IQ remained stable. Learning capacity improved. Verbal memory improved in half the subjects and declined in half, whereas figurative memory declined in most patients. Working memory and attention improved. In contrast, reaction times became longer and auditory attention span became shorter. A seizure reduction of more than 75% had been achieved in 13 (76%). Seizure control improved in five and seizures recurred in two subjects between the two- and the 10-year follow-up.