Michael Patrick Kerr

International consensus clinical practice statements for the treatment of neuropsychiatric conditions associated with epilepsy

In order to address the major impact on quality of life and epilepsy management caused by associated neuropsychiatric conditions, an international consensus group of epileptologists met with the aim of developing clear evidence‐based and practice‐based statements to provide guidance on the management of these conditions. Using a Delphi process, this group prioritized a list of key management areas. These included: depression, anxiety, psychotic disorders, nonepileptic seizures, cognitive dysfunction, antiepileptic drug (AED)–related neurobehavioral disorders, suicidality, disorders in children and adolescents, disorders in children with intellectual disability, and epilepsy surgery. Clinical practice statements were developed for each area and consensus reached among members of the group. The assessment and management of these conditions needs to combine knowledge of psychiatric disorders, knowledge of the impact of epilepsy and its treatment on psychopathology, and an ability to deliver care within epilepsy services. The aim of these statements is to provide guidance on quality care for people with epilepsy that have a range of neuropsychiatric disorders.

Compound heterozygosity and nonsense mutations in the alpha(1)-subunit of the inhibitory glycine receptor in hyperekplexia

The α1-inhibitory glycine receptor is a ligand-gated chloride channel composed of three ligand-binding α1-subunits and two structural β-subunits that are clustered on the postsynaptic membrane of inhibitory glycinergic neurons. Dominant and recessive mutations in GLRA1 subunits have been associated with a proportion of individuals and families with startle disease or hyperekplexia (MIM: 149400). Following SSCP and bi-directional di-deoxy fingerprinting mutational analysis of 22 unrelated individuals with hyperekplexia and hyperekplexia-related conditions, we report further novel missense mutations and the first nonsense point mutations in GLRA1, the majority of which localise outside the regions previously associated with dominant, disease-segregating mutations. Population studies reveal the unique association of each mutation with disease, and reveals that a proportion of sporadic hyperekplexia is accounted for by the homozygous inheritance of recessive GLRA1 mutations or as part of a compound heterozygote.

Self-discontinuation of antiepileptic medication in pregnancy: detection by hair analysis

Summary:  Purpose: Concerns over teratogenicity of antiepileptic drugs (AEDs) during pregnancy must be balanced against the risks of seizures to the mother and developing fetus. Pharmacokinetic changes and vomiting may alter drug levels, but more important may be the patients decision to stop medication before or during pregnancy. Compliance assessment traditionally relies either on self‐reporting or on AED plasma level monitoring; neither provides reliable information on drug‐taking behaviour over an extended interval (e.g., before, during, and after pregnancy).

Evaluation of the positional candidate gene CHRNA7 at the juvenile myoclonic epilepsy locus (EJM2) on chromosome 15q13-14

A previous study of 34 nuclear pedigrees segregating juvenile myoclonic epilepsy (JME) gave significant evidence of linkage with heterogeneity to marker loci on chromosome 15q13-14 close to the candidate gene CHRNA7 (Hum. Mol. Genet. 6 (1997) 1329). The aim of this work was to further evaluate the putative aetiological role of CHRNA7 in JME within the 34 families originally described, and to assess the contribution of this locus to a broader phenotype of idiopathic generalised epilepsy (IGE). Multipoint linkage analysis and intrafamilial association studies were performed with microsatellite markers that encompass both CHRNA7 and its partial duplication (CHRFAM7A). A maximum HLOD of 3.45 [alpha=0.58; (Zall=2.88, P=0.0008)] was observed 8 cM distal to D15S1360, a CHRNA7 intragenic marker. Significant exclusion lod scores were obtained across the region in 12 mixed phenotype JME/IGE families. Mutation screening of the CHRNA7 gene (and consequently exons 5-10 of CHRFAM7A) and its putative promoter sequence identified a total of 13 sequence variants across 23 of 34 JME-affected families. Two variants (c.1354G>A and c.1466C>T) are predicted to result in amino acid changes and one (IVS9+5G>A) is predicted to result in aberrant transcript splicing. However, none of the variants alone appeared either necessary or sufficient to cause JME in the families in which they occurred. In conclusion, linkage analyses continue to support the existence of a locus on chromosome 15q13-14 that confers susceptibility to JME but not to a broader IGE phenotype. Causal sequence variants in the positional candidate CHRNA7 have not been identified but the presence of multiple segmental duplications in this region raises the possibility of undetected disease-causing genomic rearrangements.

Epilepsy and Mortality: A Record Linkage Study in a U.K. Population

Summary:  Purpose: To examine patterns of mortality for a population with epilepsy compared with the nonepilepsy population.

Primary Health Care and Health Gain for People with a Learning Disability

The evidence suggests that the current delivery of primary care to people with a learning disability does not adequately meet their needs. In particular, individuals do not access adequate health promotion, are not having treatable illnesses identified and are not having more complex needs addressed. This review examines this evidence, highlights barriers to the effective delivery of health care and assesses these barriers, pilot projects and the few intervention studies published. Effective response to health needs will need a change in the working patterns of primary, secondary and social care providers. The contracting system and the move to locality‐based purchasing may be the ideal catalysts for these changes.

Learning disability and epilepsy. 1, towards common outcome measures

A major component of the population of people who have epilepsy are people with a learning disability. As a group, such individuals often have complex epilepsy which is refractory to treatment. Current available measures to assess the outcomes of therapeutic interventions in epilepsy are based on seizure frequency, seizure severity and quality-of-life measures, but have not been validated in people with a learning disability. Thus, we do not know if such measures of outcome serve the needs of this group. This review examines how able we are to assess the efficacy of our interventions to control epilepsy in people with learning disability. It is suggested that a standard data set is necessary as the basis of the assessment of any therapeutic intervention. Central components of this data set would encompass a definition of important characteristics of an individual, a description of their epilepsy and an assessment of the impact of their condition on both their own and their carers health. The approach to obtaining this information should employ a methodology which can allow for environmental influences.

Estimated cost of inpatient admissions and outpatient appointments for a population with epilepsy: a record linkage study.

Summary:  Purpose: This study describes the hospital costs for a population with epilepsy in 1 year (1999). The study was conducted in a defined geographic United Kingdom population of 424,000.

The Demand for Hospital Services for Patients with Epilepsy

Summary: Purpose: To describe the patterns of inpatient and outpatient hospital care for patients with epilepsy in our health district.

Exploring the evaluation of antiepileptic drug change in people with intellectual disabilities and high-frequency epileptic seizures: seizure control and sustained responsiveness to the environment.

PURPOSE Optimum antiepilepsy medication should be successful in reducing seizures with minimal adverse effects on the patients ability to concentrate or general level of awareness. The purpose was to investigate the potential of a method of measuring responsiveness to environmental events as a means of reflecting awareness levels among people with intellectual disabilities undergoing review of medication for high-frequency epileptic seizures. METHODS Observations of 22 participants referred to a specialist clinic were conducted three times a month over a 5-month period following the initial baseline measures and clinical intervention. Behavioral responsiveness was measured by calculating the likelihood of appropriate activity occurring given the occurrence of staff interaction. This likelihood was represented by the statistic Yules Q. Seizure frequency was also evaluated. RESULTS Participant responsiveness after drug review was similar to baseline indicating an absence of long-term adverse effects. Participants experienced a significant decrease in seizure frequency. CONCLUSION It was concluded that drug review led to seizure reduction while behavioral measurement confirmed no loss of responsiveness.