RESUMEN
WHAT IS KNOWN AND OBJECTIVE: One-third of patients with epilepsy are resistant to anti-epileptic drugs (AEDs). Drug-resistant epilepsy is believed to be multifactorial involving both genetic and non-genetic factors. Genetic variations in the ABCB1 gene encoding the drug efflux transporter, p-glycoprotein (p-gp), may influence the interindividual variability in AED response by limiting drugs from reaching their target. Phenobarbital (PB), one of the most cost-effective and widely used AEDs in developing countries, has been reported to be transported by p-gp. This study aimed to investigate the association of a genetic variant, ABCB1 3435C>T, and non-genetic factors with phenobarbital response in Thai patients with epilepsy. METHODS: One hundred and ten Thai patients with epilepsy who were treated with PB maintenance doses were enrolled in this study. Two phenotypic groups, PB-responsive epilepsy and PB-resistant epilepsy, were defined according to the International League Against Epilepsy (ILAE) criteria. Subjects were genotyped for ABCB1 3435C>T (rs1045642). Multiple logistic regression analysis was tested for the association of ABCB1 3435C>T polymorphism and non-genetic factors with PB response. RESULTS AND DISCUSSION: Sixty-two PB-responsive epilepsy subjects and 48 PB-resistant epilepsy subjects were identified. All genotype frequencies of the ABCB1 3435C>T SNP were consistent with the Hardy-Weinberg equilibrium (P > 0·05). The ABCB1 3435C>T polymorphism and type of epilepsy were associated with response to PB. Patients with PB-resistant epilepsy had a significantly higher frequency of ABCB1 3435CC genotype and had focal epilepsy more often than patients with PB-responsive epilepsy (adjusted OR = 3·962, 95% CI = 1·075-14·610, P-value = 0·039; adjusted OR = 5·936, 95% CI = 2·272-15·513, P-value < 0·001, respectively). The model explained 25·5% of the variability in response to PB (R(2) = 0·255). WHAT IS NEW AND CONCLUSION: Thai patients of ABCB1 3435CC genotype and with focal epilepsy were more often PB resistant. Those two factors partly account for the variability in Thai epilepsy patients' response to phenobarbital.
Asunto(s)
Anticonvulsivantes/farmacología , Epilepsia/tratamiento farmacológico , Fenobarbital/farmacología , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Adulto , Anticonvulsivantes/farmacocinética , Pueblo Asiatico/genética , Resistencia a Medicamentos/genética , Epilepsia/genética , Epilepsia/fisiopatología , Femenino , Variación Genética , Genotipo , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Fenobarbital/farmacocinética , Polimorfismo de Nucleótido Simple , TailandiaRESUMEN
PURPOSE: To compare the localizing value of ictal single photon emission computed tomography (SPECT) and interictal fluorodeoxyglucose-positron emission tomography (FDG-PET) in refractory occipital lobe epilepsy. METHODS: Six patients who underwent surgery for refractory epilepsy associated with pathology in the occipital lobe were retrospectively selected from records of the Austin & Repatriation Centre Comprehensive Epilepsy Programme. Interictal SPECT and PET and ictal SPECT were obtained by standard methods. All studies were read by a nuclear medicine expert blinded to clinical data except the diagnosis of epilepsy. RESULTS: Ictal SPECT showed unilateral occipital hyperperfusion in five of six cases often accompanied by temporal lobe hyperperfusion. These patterns were seen in cases with or without magnetic resonance imaging (MRI) abnormality. Interictal SPECT was not localizing in any case, in contrast to PET, which showed occipital hypometabolism in three of five studies. CONCLUSIONS: Ictal SPECT can provide novel localizing data in MRI-negative occipital lobe epilepsy. Interictal PET can provide useful localizing information, but its role in providing novel information was not demonstrated. Interictal SPECT is useful only as a baseline to aid in interpretation of ictal studies.
Asunto(s)
Epilepsias Parciales/diagnóstico por imagen , Lóbulo Occipital/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada de Emisión , Adulto , Edad de Inicio , Epilepsias Parciales/diagnóstico , Epilepsias Parciales/fisiopatología , Femenino , Fluorodesoxiglucosa F18 , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Lóbulo Occipital/anatomía & histología , Lóbulo Occipital/fisiopatología , Lóbulo Temporal/anatomía & histología , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/fisiopatologíaRESUMEN
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a newly recognized autosomal dominant partial epilepsy. We studied seizure localization and intrafamilial variation using video-EEG monitoring (VEM) and functional neuroimaging in two pairs of subjects from unrelated families. The clinical features of seizures were similar from seizure to seizure in each individual, but varied between individuals. As is often found in frontal lobe epilepsies, ictal EEG localization was imprecise in three of four cases. One patient showed a consistent left fronto-polar onset that was corroborated by congruent focal hypometabolism on interictal PET and focal hyperperfusion on ictal single photon emission computed tomography (SPECT). A second case studied with ictal SPECT showed a right parasagittal, midfrontal focus. We conclude that this autosomal dominant epilepsy syndrome, which in one of the two families was due to a known neuronal nicotinic acetylcholine receptor mutation, causes frontal lobe foci that are unilateral and in variable locations in different individuals.