Epilepsy Panel Research Articles

Chinese cases of early infantile epileptic encephalopathy: a novel mutation in the PCDH19 gene was proved in a mosaic male- case report

BackgroundThe link between the protocadherin-19 (PCDH19) gene and epilepsy suggests that an unusual form of X-linked inheritance affects females but is transmitted through asymptomatic males. Individuals with epilepsy associated with mutations in the PCDH19 gene display generalized or focal seizures with or without fever sensitivity. The clinical manifestation of the condition ranges from mild to severe, resulting in intellectual disability and behavioural disturbance. In the present study, we assessed mutations in the PCDH19 gene and the clinical features of a group of Chinese patients with early infantile epileptic encephalopathy and aimed to provide further insight into the understanding of epilepsy and mental retardation limited to females (EFMR; MIM 300088).Case PresentationWe described three variations in the PCDH19 gene in Chinese patients with epilepsy who developed generalized seizures occurring in clusters with or without triggering by fever. Candidate genes were screened for mutations that cause epilepsy and related paroxysmal or nervous system diseases in the coding exons and intron–exon boundaries using polymerase chain reaction (PCR) of genomic deoxyribonucleic acid (DNA) followed by sequencing. The variations were sequenced using next-generation sequencing technology and verified with first-generation sequencing. Exome sequencing of a multigene epilepsy panel revealed three mutations in the PCDH19 gene in a mosaic male and two unrelated females. These included a frameshift mutation c.1508_1509insT (p.Thr504HisfsTer19), a missense mutation c.1681C > T (p.Pro561Ser) and a nonsense mutation c.918C > G (p.Tyr306Ter). Of the three mutations in the PCDH19 gene associated with early infantile epileptic encephalopathy, the frameshift variation in a mosaic male is novel and de novo, the missense variation is de novo and is the second ever reported in females, and the nonsense variation was inherited from the paternal line and is the first example discovered in a female.ConclusionsThe results from our current study provide new insight into and perspectives for the molecular genetic link between epilepsy and PCDH19 alterations. Moreover, our new findings of the male mosaic variant broaden the spectrum of PCDH19-related epilepsy and provide a new understanding of this complex genetic disorder.

GAD65 antibody‐associated autoimmune epilepsy with unique independent bitemporal‐onset ictal asystole

Antibodies against the 65-kDa isoform of the intracellular enzyme, glutamate decarboxylase (GAD65), have been found in patients with limbic encephalitis and drug-resistant autoimmune epilepsy. We report a 22-year-old female who presented with new-onset seizures and neuropsychiatric symptoms. Video-EEG captured unique, independent bitemporal-onset focal seizures with impaired awareness and ictal asystole. An autoimmune epilepsy panel revealed elevated GAD65 antibodies in the serum (225nmol/l) and CSF (2.78nmol/l), while [18F]-fluoro-deoxy-glucose positron emission tomography showed bitemporal hypometabolism (left > right). The patient was diagnosed with GAD65 antibody-associated autoimmune epilepsy. Our observation adds to the spectrum of neurocardiac syndromes associated with autoimmune epilepsy.

Retrospective genotype-phenotype analysis in a 305 patient cohort referred for testing of a targeted epilepsy panel

PurposeEpilepsy is a diverse neurological condition with extreme genetic and phenotypic heterogeneity. The introduction of next-generation sequencing into the clinical laboratory has made it possible to investigate hundreds of associated genes simultaneously for a patient, even in the absence of a clearly defined syndrome. This has resulted in the detection of rare and novel mutations at a rate well beyond our ability to characterize their effects. This retrospective study reviews genotype data in the context of available phenotypic information on 305 patients spanning the epileptic spectrum to identify established and novel patterns of correlation. MethodsOur epilepsy panel comprising 377 genes was used to sequence 305 patients referred for genetic testing. Qualifying variants were annotated with phenotypic data obtained from either the test requisition form or supporting clinical documentation. Observed phenotypes were compared with established phenotypes in OMIM, published literature and the ILAEs 2010 report on genetic testing to assess congruity with known gene aberrations. ResultsWe identified a number of novel and recognized genetic variants consistent with established epileptic phenotypes. Forty-one pathogenic or predicted deleterious variants were detected in 39 patients with accompanying clinical documentation. Twenty-five of these variants across 15 genes were novel. Furthermore, evaluation of phenotype data for 194 patients with variants of unknown significance in genes with autosomal dominant and X-linked disease inheritance elucidated potentially disease-causing variants that were not currently characterized in the literature. ConclusionsAssessment of key genotype-phenotype correlations from our cohort provide insight into variant classification, as well as the importance of including ILAE recommended genes as part of minimum panel content for comprehensive epilepsy tests. Many of the reported VUSs are likely genuine pathogenic variants driving the observed phenotypes, but not enough evidence is available for assertive classifications. Similar studies will provide more utility via mounting independent genotype-phenotype data from unrelated patients. The possible outcome would be a better molecular diagnostic product, with fewer indeterminate reports containing only VUSs.

S14. PURA (Purine-Rich Element Binding Protein A) syndrome

Introduction Burst suppression is an electroencephalographic (EEG) pattern characterized by a brief interval of relatively high voltage activity with intervening periods of generalized suppression. It is commonly seen consequent to anoxic brain injury, deep coma states, encephalopathies or hypothermia. This pattern is differentiated from trace discontinua because of longer interburst interval and higher amplitude during bursts. Myotonic discharges (M.D.) seen in an electromyographic (EMG) study are the abnormal wave of excitation due to the firing of repetitive action potentials. It is characterized by waveforms with alternating frequency and amplitude. This unique pattern is seen in muscular dystrophies, muscle channelopathies, toxic or inflammatory myopathies. We report a case of PURA syndrome with significant EEG findings of burst suppression and EMG pattern of myotonic discharges which has not been described in literature before. Methods A male infant was born at 37-week gestation via spontaneous vaginal delivery to a 35-year-old G1P0 after an uneventful pregnancy. At birth, the infant was observed to have generalized central hypotonia and seizure-like spells of posturing, lip-smacking and blinking lasting for 10–15 s. Family history was unremarkable. A video EEG and EMG were ordered for futher evaluation, in addition to other routine testing. Results Video EEG demonstrated excessive multifocal sharps and periods of burst suppression. EMG study reported myotonic discharges in the first dorsal interosseous and tibialis anterior. Work up for metabolic etiologies were negative. CSF studies, chromosomal studies, infantile epilepsy panel, myotonic dystrophy panel were unremarkable. Whole exome sequencing was significant for a de novo mono-allelic mutation of the PURA gene (variant PR245X, coding DNA c.733 C > T). Conclusion PURA (purine-rich element binding protein A) syndrome is a genetic disorder caused by a gene deletion in 5q31.3, characterized by neonatal hypotonia, seizures and intellectual disability. It leads to an alteration in the PURA protein, affecting the protein’s DNA regulatory function. All reported deletions have been de novo. Therefore the risk of future inheritance of this genetic mutation is low. PURA Syndrome is known to cause epilepsy in 54% of previously reported patients. In our case, the patient’s EEG pattern was consistent with burst suppression, which supports the fact that PURA Syndrome is a state of generalized brain dysfunction. EMG reports were consistent with myotonic discharges. The significance of this finding in our patient is unclear and requires further research to characterize EMG findings in affected patients with PURA syndrome. This case however underscores the importance of considering PURA syndrome in the differential diagnosis of neonatal EEG findings of burst suppression pattern and EMG findings of myotonic discharge.

T18. High dose phenobarbital is safe and effective treatment for SCN2A related epilepsy

Introduction Voltage-gated sodium channels play major role in neuronal excitability. Nav1.1, Nav1.2, Nav1.3 and Nav1.6 sodium channels found in the brain differ in α -subunits, encoded by SCN1A, SCN2A, SCN3A, and SCN8A genes respectively. NaV1.2 Channels is the only sodium channel expressed during early development at nodes of Ranvier and in the axon initial segment (AIS) in developing and mature neurons, particularly cortical glutamatergic pyramidal cells. NaV1.2 channel has relatively high exictation threshold. NaV1.2 is regulated developmentally by alternative splicing to produce ‘neonatal’ and ‘adult’ isoforms. ‘Neonatal’ form is less excitable than ‘adult’ conferring reduced neuronal excitability and seizure susceptibility. Most dominantly inherited missense genetic variants of NaV1.2 manifests as familial epilepsy while de novo mutations as severe epileptic encephalopathy, both have gain of function with increased excitability and lowered seizure threshold. Cortical pyramidal neurons AIS receives exclusively inhibitory GABA-ergic input from specific set of interneurons called chandelier cells. Methods A FT, WF child born via planned caesarian to a healthy 27 yr G2P2A0L2 with APGAR 8, 9 at 1, 5 min at OSH. On DOL 2, developed seizure manifested as chocking, left arm forced flexion with leftward head deviation, right arm extension evolve into whole body jerking with apnea. Ictal EEG documented left frontal-temporal onset focal seizure. She received two loading doses of Phenobarbital followed by maintenance of 5 mg/kg/day. At therapeutic level of 44 mcg/ml, seizures remained under controlled. On DOL 22, presented to OSH with right arm twitching. Random PHB level was 27.5 mcg/ml. She received load of PHB and Levetiracetam 20 mg/kg each. Seizures continued overnight leading to transfer to our institute. Patient physcial and neurologic exam was normal. Ictal EEG re-demonstrated left central onset rhythmic spike-wave seizure evolution pattern clinically manifesting wide-eyed gaze with right face and upper extremity clonic jerking. Patient received total dose of 40 mg/kg of levetiracetam without improvement. Later, two 10 mg/kg doses of PHB given at couple of hours interval stopped seizures. Maintenance dosing of PHB was increased to 6 mg/kg/day. PHB level obtained was 54.2mcg/ml. It was tolerated well without sedation, hypotonia or adverse effects. She has been weaned off PHB at 7 months of age and has been seizure free with normal development at 14 months of age. Gene DX Comprehensive Epilepsy Panel revealed pathogenic variant of the SCN2A gene (p. Val261Met). Results We described infant with de novo SCN2A mutation presenting as benign familial neonatal infantile epilepsy well controlled with high therapeutic phenobarbital level without experiencing adverse side effects. Conclusion Phenobarbital at very high therapeutic level exerted seizure control probably via inhibitory effects of Chanderlier cell counterbalancing increased excitability of genetic missense variant of NaV1.2 at the AIS.

High frequency of mosaic pathogenic variants in genes causing epilepsy-related neurodevelopmental disorders

PurposeMosaicism probably represents an underreported cause of genetic disorders due to detection challenges during routine molecular diagnostics. The purpose of this study was to evaluate the frequency of mosaicism detected by next-generation sequencing in genes associated with epilepsy-related neurodevelopmental disorders.MethodsWe conducted a retrospective analysis of 893 probands with epilepsy who had a multigene epilepsy panel or whole-exome sequencing performed in a clinical diagnostic laboratory and were positive for a pathogenic or likely pathogenic variant in one of nine genes (CDKL5, GABRA1, GABRG2, GRIN2B, KCNQ2, MECP2, PCDH19, SCN1A, or SCN2A). Parental results were available for 395 of these probands.ResultsMosaicism was most common in the CDKL5, PCDH19, SCN2A, and SCN1A genes. Mosaicism was observed in GABRA1, GABRG2, and GRIN2B, which previously have not been reported to have mosaicism, and also in KCNQ2 and MECP2. Parental mosaicism was observed for pathogenic variants in multiple genes including KCNQ2, MECP2, SCN1A, and SCN2A.ConclusionMosaic pathogenic variants were identified frequently in nine genes associated with various neurological conditions. Given the potential clinical ramifications, our findings suggest that next-generation sequencing diagnostic methods may be utilized when testing these genes in a diagnostic laboratory.

Early-Life Epilepsies and the Emerging Role of Genetic Testing

ImportanceEarly-life epilepsies are often a consequence of numerous neurodevelopmental disorders, most of which are proving to have genetic origins. The role of genetic testing in the initial evaluation of these epilepsies is not established.ObjectiveTo provide a contemporary account of the patterns of use and diagnostic yield of genetic testing for early-life epilepsies.Design, Setting, and ParticipantsIn this prospective cohort, children with newly diagnosed epilepsy with an onset at less than 3 years of age were recruited from March 1, 2012, to April 30, 2015, from 17 US pediatric hospitals and followed up for 1 year. Of 795 families approached, 775 agreed to participate. Clinical diagnosis of the etiology of epilepsy were characterized based on information available before genetic testing was performed. Added contributions of cytogenetic and gene sequencing investigations were determined. ExposuresGenetic diagnostic testing.Main Outcomes and MeasuresLaboratory-confirmed pathogenic variant.ResultsOf the 775 patients in the study (367 girls and 408 boys; median age of onset, 7.5 months [interquartile range, 4.2-16.5 months]), 95 (12.3%) had acquired brain injuries. Of the remaining 680 patients, 327 (48.1%) underwent various forms of genetic testing, which identified pathogenic variants in 132 of 327 children (40.4%; 95% CI, 37%-44%): 26 of 59 (44.1%) with karyotyping, 32 of 188 (17.0%) with microarrays, 31 of 114 (27.2%) with epilepsy panels, 11 of 33 (33.3%) with whole exomes, 4 of 20 (20.0%) with mitochondrial panels, and 28 of 94 (29.8%) with other tests. Forty-four variants were identified before initial epilepsy presentation. Apart from dysmorphic syndromes, pathogenic yields were highest for children with tuberous sclerosis complex (9 of 11 [81.8%]), metabolic diseases (11 of 14 [78.6%]), and brain malformations (20 of 61 [32.8%]). A total of 180 of 446 children (40.4%), whose etiology would have remained unknown without genetic testing, underwent some testing. Pathogenic variants were identified in 48 of 180 children (26.7%; 95% CI, 18%-34%). Diagnostic yields were greater than 15% regardless of delay, spasms, and young age. Yields were greater for epilepsy panels (28 of 96 [29.2%]; P < .001) and whole exomes (5 of 18 [27.8%]; P = .02) than for chromosomal microarray (8 of 101 [7.9%]).Conclusions and RelevanceGenetic investigations, particularly broad sequencing methods, have high diagnostic yields in newly diagnosed early-life epilepsies regardless of key clinical features. Thorough genetic investigation emphasizing sequencing tests should be incorporated into the initial evaluation of newly presenting early-life epilepsies and not just reserved for those with severe presentations and poor outcomes.

Clinical utility of a 377 gene custom next-generation sequencing epilepsy panel.

Epilepsy is one of the most common neurological disorders with about 500 genes thought to be involved across the phenotypic spectrum (Busch et al. 2014; Ran et al. 2014), which includes monogenic, multigenic, epistatic and pleiotropic phenotype manifestations (Busch et al. 2014; Thomas et al. 2014), driving the need for a comprehensive diagnostic test. Next-generation sequencing (NGS) allows for the simultaneous investigation of a large number of genes, making it a very attractive option for a condition as diverse as epilepsy at a low cost compared to traditional Sanger sequencing (Lemke et al. 2012; Németh et al. 2013). Our 377 gene epilepsy NGS test was developed to include genes known to cause or have published association with epilepsy and seizure-related disorders. Given the scale of information that is generated, the efficacy of an NGS panel depends on a number of factors, including the genes present on the panel, prebioinformatic and postbioinformatic analysis protocols, as well as reporting criteria, prompting the current study, a retrospective analysis of 305 cases tested for the epilepsy panel.

Genetic and immune findings in complex febrile seizures and the epidemiology of Dravet syndrome: A nationwide cohort study.

Objectives: To determine what proportion of children presenting with complex febrile seizures (CFS) have an identifiable genetic mutation and/or serum anti-neuronal autoantibody positivity. To calculate the incidence of SCN1A-positive Dravet syndrome in Scotland. Methods: Patients were recruited from all 21 acute paediatric centres in the Scottish National Health Service over three-years (2014-2017). All children aged under three years (<3y) presenting with CFS were eligible. CFS was defined as any of: a cluster of two or more febrile seizures within a 24-hour period; any episode of febrile status epilepticus; two or more prolonged (>10 minute) febrile seizures within any time period. All children <3y presenting with new-onset epilepsy (n=167), afebrile status epilepticus (n= 6), or clusters of afebrile seizures (n=5) were recruited as a comparison group. All recruits had testing on a 104-gene epilepsy panel and serum antibodies to 10 neuronal epitopes (AMPA, CASPR2, GABAa, GABAb, Glycine, LGI1, NMDA, TAG, GAD,V GKC). Results: In 32 months, 70/260 (27%) of total recruited cases fulfilled our criteria for CFS, equal to 7% of total first febrile seizure presentations (400 per year in Scotland). Gene panel testing identified a pathogenic mutation in 6 CFS cases (8.6%). In all 6 the causative gene was SCN1A. A further 4 cases of SCN1A mutation were identified from the cohort presenting with epilepsy without antecedent febrile seizures. 9/10 SCN1A-positive cases had a clinical picture consistent with Dravet syndrome, making the incidence of SCN1A- positive Dravet syndrome in this population 1 in 16,600 live births. Anti-neuronal antibodies were identified in 10% of the CFS cohort, versus 14% of the epilepsy cohort. One of 10 SCN1A-positive patients also had antibodies(GABAa). Conclusion: The only major genetic epilepsy presenting initially with CFS is SCN1A- related. Most SCN1A-related epilepsy cases present initially with febrile seizures, but 40% have initial seizures that are afebrile. The incidence of SCN1A-positive Dravet syndrome is higher than previously reported.

Phenotype is not Always a Positive Predictor of Detection Rate in Epilepsy Panels (P1.231)

Phenotype is not Always a Positive Predictor of Detection Rate in Epilepsy Panels (P1.231)

Childhood-Onset Epileptic Encephalopathy Associated With Isolated Focal Cortical Dysplasia and a Novel TSC1 Germline Mutation.

Tuberous sclerosis complex (TSC) is an autosomal-dominant inheritable neurocutaneous disease due to mutations within the TSC1 and TSC2 genes. Many patients present with West syndrome, a severe epilepsy syndrome characterized by the triad of infantile spasms, an interictal electroencephalogram (EEG) pattern termed hypsarrhythmia (continuous slow activity with an amplitude higher than 300 µV and multiregional spikes/polyspikes/sharp waves) and developmental regression. In this study, we report on a previously healthy patient with positive family history of epilepsy with new-onset epileptic encephalopathy at the age of 9 years. Clinical signs alone were not sufficient to establish the diagnosis of TSC but epilepsy panel screening revealed a novel frameshift mutation (c.90delA; p.Glu31Argfs*12) within the TSC1 gene. Segregation gene analysis detected the same mutation in the mother. Cranial magnetic resonance imaging (MRI) studies from the index patient and his mother revealed a similar pattern of isolated subcortical white matter lesions resembling most likely focal cortical dysplasia (FCD) type IIb. In summary, in these 2 related patients, a novel TSC1 frameshift mutation was associated with an isolated FCD type IIb in the absence of further CNS abnormalities usually encountered in patients with TSC, fostering our understanding of the broad mutation spectra in the TSC1 gene and the close relationship between cortical tubers and FCD type IIb.

De novo and inherited SCN8A epilepsy mutations detected by gene panel analysis

ObjectivesTo determine the incidence of pathogenic SCN8A variants in a cohort of epilepsy patients referred for clinical genetic testing. We also investigated the contribution of SCN8A to autism spectrum disorder, intellectual disability, and neuromuscular disorders in individuals referred for clinical genetic testing at the same testing laboratory. MethodsSequence data from 275 epilepsy panels screened by Emory Genetics Laboratory were reviewed for variants in SCN8A. Two additional cases with variants in SCN8A were ascertained from other testing laboratories. Parental samples were tested for variant segregation and clinical histories were examined. SCN8A variants detected from gene panel analyses for autism spectrum disorder, intellectual disability, and neuromuscular disorders were also examined. ResultsFive variants in SCN8A were identified in five individuals with epilepsy. Three variants were de novo, one was inherited from an affected parent, and one was inherited from an unaffected parent. Four of the individuals have epilepsy and developmental delay/intellectual disability. The remaining individual has a milder epilepsy presentation without cognitive impairment. We also identified an amino acid substitution at an evolutionarily conserved SCN8A residue in a patient who was screened on the autism spectrum disorder panel. Additionally, we examined the distribution of pathogenic SCN8A variants across the Nav1.6 channel and identified four distinct clusters of variants. These clusters are primarily located in regions of the channel that are important for the kinetics of channel inactivation. ConclusionsVariants in SCN8A may be responsible for a spectrum of epilepsies as well as other neurodevelopmental disorders without seizures. The predominant pathogenic mechanism appears to involve disruption of channel inactivation, leading to gain-of-function effects.

Diagnostic Yield of Epilepsy Panels in Children With Medication-Refractory Epilepsy

BackgroundWhen no chromosomal variations are identified, patients with suspected genetic etiologies can be tested using next-generation sequencing utilizing epilepsy panels. The primary objective of this study was to analyze the diagnostic yield of next-generation sequencing epilepsy panels in medication-resistant epilepsy subjects with non–clinically significant comparative genomic hybridization microarray results. MethodsWe completed a single-center retrospective review of the diagnostic yield of next-generation sequencing epilepsy panels in medication-resistant epilepsy subjects aged 18 years or less who had non–clinically significant comparative genomic hybridization microarray results from January 2011 to December 2014. The primary end point was the yield of clinically significant next-generation sequencing results. ResultsForty-nine subjects (21 male) with medication-refractory epilepsy and clinically in significant comparative genomic hybridization microarray results were identified. Next-generation sequencing abnormalities were seen in 28 subjects (57%): seven of these 28 subjects (25%) had clinically significant findings. Mutations were found in the SCN1A gene in three subjects, in the PCDH19 gene in two subjects, and in DLG3, MECP2, TSC2, and SLC9A6 genes in one subject each. Only the MECP2 mutation was found to be pathogenic in this last subject. The additional yield of next-generation sequencing with uninformative chromosomal microarray was 14%. Positive findings were primarily seen in those with Dravet syndrome, all with SCN1A mutations (42% of clinically significant results). Given the small sample size, a larger prospective study would help to determine the clinical yield of next-generation sequencing. ConclusionNext-generation sequencing seizure panels could be a useful tool in the diagnosis of nonacquired pediatric medication-refractory epilepsy with uninformative comparative genomic hybridization microarray.

27 - Rare Focal Deletions Involving SNRPN and UBE3A Genes

Prader-Willi (PWS) and Angelman (AS) syndromes are genetic disorders with multiple well-known mechanisms. Approximately 70% of individuals with PWS or AS have a ~4 Mb deletion of 15q11-q13, while the remainder have UPD15, an imprinting defect or, in the case of UBE3A, a sequence variant. Rarely have focal deletions been reported. We report here on three such unusual cases from our clinical microarray experience. Case 1 was a 2-1/2 year old boy with global developmental delay, short stature, microcephaly, failure to thrive and possible hearing loss. This boy, his healthy mother and maternal grandfather had a 36 kb deletion involving only noncoding exons 1 and 2 of UBE3A (NM_130839). Although previously unreported, this deletion is considered likely pathogenic based upon the AS phenotype in the proband and the inheritance pattern in this family. Case 2 was a 2-1/2 year old girl with epilepsy referred for testing on our childhood epilepsy panel which includes sequencing and copy number analysis of 58 relevant genes. Exon-level array showed an intragenic deletion of exons 2–4 of UBE3A. Methylation -specific MLPA (MS-MLPA) showed normal imprinting. Parental testing may be informative in assisting diagnosis since only maternal inheritance would be consistent with AS. Case 3 was the phenotypically normal father of a boy with PWS and a known SNRPN deletion. Array showed that the father had a 109 kb deletion of exons 4–12 of SNRPN (NM_022808) as well as the upstream reading frame (SNURF). MS-MLPA showed that this deletion was on the maternally derived chromosome. Although rare, intragenic or gene deletion of either UBE3A or SNRPN rather than the common 4 Mb deletion can be observed with PWS and AS. An assay which provides exon level coverage of these genes is important when interrogating this region.

Review of Commercially Available Epilepsy Genetic Panels.

Next generation sequencing panels have revolutionized the diagnostic approach to patients with epilepsy. There are several commercial epilepsy panels available. We assessed the list of genes tested and consent forms for epilepsy panels available at seven laboratories. The panels varied in the number of genes included (70-465 genes). In some panels, genes not currently associated with epilepsy were included (up to 4 % of panel content). The panels also included genes for lysosomal storage disorders (6-12 %), congenital disorders of glycosylation (0-8.5 %), metabolic disorders (3.5-34 %), neurological syndromes (18-43 %) and multisystemic genetic syndromes (6.4-21 %). Informed consents differed significantly between laboratories ranging from basic information about genetic testing and possible results to information about insurance, genetic counseling and familial testing, and incidental findings.Our findings suggest that it is important to consider the range of genes offered on epilepsy panels and their predicted phenotypes in an effort toward improving the informed consent process.

Attitudes of GPs to the care of people with epilepsy.

Most individuals with current epilepsy are solely under the care of the primary care team for follow-up care. Government working party recommendations, expert epilepsy panels and patients have also stressed the central role of the GP in follow-up care. Problems in the provision of care in the community have, however, repeatedly been highlighted. The views of GPs about service provision for people with epilepsy may be an important barrier to providing care, but have not yet been studied in a systematic manner. We aimed to ascertain the views of GPs on service provision for people with epilepsy in primary care and on specific initiatives to improve care. A specially designed postal questionnaire was sent to all 262 GPs on the list of West Glamorgan FHSA. It ascertained what GPs felt their role should be in providing care to people with epilepsy, identified their views on the importance of particular problems in providing this care, as well as obtaining their opinions on possible future initiatives to improve epilepsy care in the community. The overall response rate was 70%. Although a majority of responding GPs (55%) agreed that the care of people with epilepsy should be based in general practice, 23% disagreed. A lack of confidence about knowledge of epilepsy (34% responders), unfamiliarity with new drugs (65% responders) and a lack of time (41% responders) were identified as important perceived barriers to providing epilepsy care. Nearly all responding GPs would welcome guidelines for epilepsy care (93% felt they would be very helpful) and an epilepsy liaison nurse in the community was the most popular option in terms of preferred overall strategy for improving care. Despite 40 years of official recommendations regarding the central role of the GP in the follow-up care of people with epilepsy, a number of GPs have difficulty in providing this care. Many feel that they lack knowledge or are too time pressured to improve the situation. Nearly all GPs say that they would find guidelines for epilepsy care very helpful and over half would find epilepsy liaison nurses helpful. There is scope for more innovative ideas for epilepsy care in the community.