Ingrid Olsson

Clinical and aetiological aspects of epilepsy in children with cerebral palsy.

The aims of this retrospective and population‐based study were to describe the frequency and characteristics of epilepsy in 146 children (82 males and 64 females) with cerebral palsy (CP) born from 1987 to 1994 in the Göteborg area of Sweden. The frequency of epilepsy was found to be 38% (55 children). All children with tetraplegic CP and about one‐third of the children with other CP types developed epilepsy. Age at onset of epilepsy varied with type of CP: children with tetraplegic CP tended to have an earlier onset of epilepsy than children with other CP types. Partial seizures were the most common seizure type; all children with hemiplegic CP had partial seizures. Children with cognitive impairment had a higher frequency of epilepsy than those without cognitive impairment. CP aetiology may predict the development and outcome of epilepsy, as children with CP caused by CNS malformation, CNS infection, and grey matter damage all showed a higher frequency of epilepsy than children with CP of other aetiology, and also had less chance of becoming seizure‐free.

Behaviour in Children with Cerebral Palsy with and without Epilepsy.

The aim of the study was to describe behavioural problems in children with cerebral palsy (CP) with and without epilepsy. The children were sampled from the Western Sweden CP register and were part of a European Union project. The Strength and Difficulties Questionnaire and questions on epilepsy were answered by one parent of each child. Medical records were reviewed. Parents of 83 children (44 males, 39 females) age range participated: 30 at Gross Motor Function Classification System levels I and II, and 53 at levels III to V; 60 had spastic age range 8 to 12 years (bilateral 42, unilateral 18) and 23 dyskinetic CP; 34 children had active epilepsy. The proportion of children with normal behaviour on the total difficulties score (TDS) of the Strength and Difficulties Questionnaire was significantly lower than normative data (57% vs 80%, p<0.001). Parents of 21 children (25%) considered their child’s behaviour to be abnormal. Children with CP and epilepsy had a significantly higher median TDS (p=0.03) than seizure‐free children. In children with aided or no walking ability, the TDS was significantly higher in those with epilepsy (p=0.04). Parents of 32 children (39%) considered their children’s behaviour to have an impact on themselves and others. We conclude that behavioural problems are common in children with CP, and even more when epilepsy is present. Parents identify these problems, and professionals need to address them.

Lack of effects of vagus nerve stimulation on drug-resistant epilepsy in eight pediatric patients with autism spectrum disorders: A prospective 2-year follow-up study

Vagus nerve stimulation (VNS) therapy has been reported to reduce seizure frequency in some children with drug-resistant epilepsy who are not suitable candidates for epilepsy surgery. It has been suggested that there may be positive cognitive and/or behavioral effects independent of seizure control. We describe the effects of VNS with respect to seizure frequency, cognition, and autistic symptoms and behavior in eight children and adolescents with medically intractable epilepsy and autism. In comparison to baseline, seizure frequency had not decreased in anyone in our series at the 2-year follow-up. In three cases, minor improvements in general functioning were noted, but there were no positive cognitive effects. This open prospective pilot study highlights the need for more prospective studies to prevent false expectations of improvement in this severely disabled group.

Psychopathology, psychosocial functioning, and IQ before and after epilepsy surgery in children with drug-resistant epilepsy

This is a prospective study of a consecutive series of children undergoing epilepsy surgery. The main aims were to evaluate the heterogeneity with respect to psychopathology and IQ, and to use a global assessment scale (Childrens Global Assessment Scale [CGAS]) to evaluate psychosocial functioning. Clinical neuropsychiatric and neuropsychological assessments were made at baseline and at the 2-year follow-up in 24 patients, and changes were analyzed at an individual level. Psychiatric disorders (mainly attention deficit hyperactivity disorder and/or autism spectrum disorders) were found in 17 of 24 at some point. All except one child with psychiatric diagnoses before surgery still had at least one diagnosis at follow-up. Intellectual ability remained stable in the majority of cases, both in individuals with and in individuals without mental retardation. The CGAS illustrated the consequences of the extensive comorbidity in this cohort. The behavioral problems had been undiagnosed despite parental concern in many cases, indicating an unrecognized need for services for children with drug-resistant epilepsy.

Evaluation of CACNA1H in European patients with childhood absence epilepsy

CACNA1H was evaluated in a resource of Caucasian European patients with childhood absence epilepsy by linkage analysis and typing of sequence variants previously identified in Chinese patients. Linkage analysis of 44 pedigrees provided no evidence for a locus in the CACNA1H region and none of the Chinese variants were found in 220 unrelated patients.

Temporal Lobe Resections in Children with Epilepsy: Neuropsychiatric Status in Relation to Neuropathology and Seizure Outcome.

The purpose of this work was to relate clinical neuropsychiatric findings to histopathological diagnoses and seizure outcome in a retrospective study of 16 children undergoing temporal lobe resections due to medically intractable epilepsy. These children constitute a heterogeneous group in which neuropsychiatric symptoms were common. The results of this study indicate a correlation between malformations of cortical development, less chance of seizure freedom, and neuropsychiatric problems in children with pharmacoresistant temporal lobe epilepsy. It is important to include neuropsychiatric assessments pre- and postoperatively and to inform parents that symptoms of autism spectrum disorders may or may not be improved after epilepsy surgery.

Linkage and association analysis of CACNG3 in childhood absence epilepsy.

Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy characterised by absence seizures manifested by transitory loss of awareness with 2.5–4 Hz spike–wave complexes on ictal EEG. A genetic component to aetiology is established but the mechanism of inheritance and the genes involved are not fully defined. Available evidence suggests that genes encoding brain expressed voltage-gated calcium channels, including CACNG3 on chromosome 16p12–p13.1, may represent susceptibility loci for CAE. The aim of this work was to further evaluate CACNG3 as a susceptibility locus by linkage and association analysis. Assuming locus heterogeneity, a significant HLOD score (HLOD=3.54, α=0.62) was obtained for markers encompassing CACNG3 in 65 nuclear families with a proband with CAE. The maximum non-parametric linkage score was 2.87 (P<0.002). Re-sequencing of the coding exons in 59 patients did not identify any putative causal variants. A linkage disequilibrium (LD) map of CACNG3 was constructed using 23 single nucleotide polymorphisms (SNPs). Transmission disequilibrium was sought using individual SNPs and SNP-based haplotypes with the pedigree disequilibrium test in 217 CAE trios and the 65 nuclear pedigrees. Evidence for transmission disequilibrium (P≤0.01) was found for SNPs within a ∼35 kb region of high LD encompassing the 5’UTR, exon 1 and part of intron 1 of CACNG3. Re-sequencing of this interval was undertaken in 24 affected individuals. Seventy-two variants were identified: 45 upstream; two 5’UTR; and 25 intronic SNPs. No coding sequence variants were identified, although four variants are predicted to affect exonic splicing. This evidence supports CACNG3 as a susceptibility locus in a subset of CAE patients.

Estimation of Renal Function in Children and Adolescents With Spinal Dysraphism

PURPOSE In children with spinal dysraphism such as myelomeningocele the relation between muscle mass and body composition varies considerably. Therefore, it is difficult to evaluate the relevance of renal function assessments done with serum creatinine. Since serum cystatin C has been suggested to be independent of body size and composition, this evaluation was compared to chromium(51) edetic acid clearance. MATERIALS AND METHODS Simultaneous measurements of cystatin C and chromium(51) edetic acid clearance were performed prospectively in 65 patients 2 to 19 years old with spinal dysraphism. RESULTS Cystatin C values were within the normal range in all patients, while chromium(51) edetic acid clearance was reduced in 10. A significant relation was seen. CONCLUSIONS Using chromium(51) edetic acid clearance as a gold standard, children with spinal dysraphism and slightly to moderately reduced renal function may remain undiagnosed if cystatin C is used for evaluation.