RESUMEN
Generalized tonic-clonic seizures (GTCS) are the severest and most remarkable clinical expressions of human epilepsy. Cortical, subcortical, and cerebellar structures, organized with different network patterns, underlying the pathophysiological substrates of genetic associated epilepsy with GTCS (GE-GTCS) and focal epilepsy associated with focal to bilateral tonic-clonic seizure (FE-FBTS). Structural covariance analysis can delineate the features of epilepsy network related with long-term effects from seizure. Morphometric MRI data of 111 patients with GE-GTCS, 111 patients with FE-FBTS and 111 healthy controls were studied. Cortico-striato-thalao-cerebellar networks of structural covariance within the gray matter were constructed using a Winner-take-all strategy with five cortical parcellations. Comparisons of structural covariance networks were conducted using permutation tests, and module effects of disease duration on networks were conducted using GLM model. Both patient groups showed increased connectivity of structural covariance relative to controls, mainly within the striatum and thalamus, and mostly correlated with the frontal, motor, and somatosensory cortices. Connectivity changes increased as a function of epilepsy durations. FE-FBTS showed more intensive and extensive gray matter changes with volumetric loss and connectivity increment than GE-GTCS. Our findings implicated cortico-striato-thalamo-cerebellar network changes at a large temporal scale in GTCS, with FE-FBTS showing more severe network disruption. The study contributed novel imaging evidence for understanding the different epilepsy syndromes associated with generalized seizures.
Asunto(s)
Cerebelo , Corteza Cerebral , Cuerpo Estriado , Epilepsia Tónico-Clónica , Síndromes Epilépticos , Sustancia Gris , Red Nerviosa , Tálamo , Adulto , Cerebelo/diagnóstico por imagen , Cerebelo/patología , Cerebelo/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Conectoma , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/patología , Cuerpo Estriado/fisiopatología , Epilepsia Tónico-Clónica/diagnóstico por imagen , Epilepsia Tónico-Clónica/patología , Epilepsia Tónico-Clónica/fisiopatología , Síndromes Epilépticos/diagnóstico por imagen , Síndromes Epilépticos/patología , Síndromes Epilépticos/fisiopatología , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Sustancia Gris/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/patología , Red Nerviosa/fisiopatología , Tálamo/diagnóstico por imagen , Tálamo/patología , Tálamo/fisiopatología , Adulto JovenRESUMEN
OBJECTIVES: Our aim was to investigate regional difference in brain activities in response to antiepileptic drug (AED) medications in benign epilepsy with central-temporal spikes (BECTS) using resting-state functional magnetic resonance imaging (fMRI). METHODS: Fifty-seven patients with BECTS underwent resting-state fMRI scans after receiving either valproic acid (VPA) (n = 15), levetiracetam (LEV) (n = 21), or no medication (n = 21). fMRI regional homogeneity (ReHo) parameter among the three groups of patients were compared and were correlated with total doses of AED in the two medicated groups. RESULTS: Compared with patients on no-medication, patients receiving either VPA or LEV showed decreased ReHo in the central-temporal region, frontal cortex, and thalamus. In particular, the VPA group showed greater ReHo decrease in the thalamus and milder in cortices and caudate heads compared with the LEV group. In addition, the VPA group demonstrated a negative correlation between ReHo values in the central-temporal region and medication dose. CONCLUSION: Both VPA and LEV inhibit resting-state neural activity in the central-temporal region, which is the main epileptogenic focus of BECTS. VPA reduced brain activity in the cortical epileptogenic regions and thalamus evenly, whereas LEV reduced brain activity predominantly in the cortices. Interestingly, VPA showed a cumulative effect on inhibiting brain activity in the epileptogenic regions in BECTS. KEY POINTS: ⢠Regional differences in brain activity in response to different AEDs in BECTS. ⢠AEDs inhibit resting-state neural activity in epileptogenic and subcortical regions in BECTS. ⢠Valproic acid effect on the cortical epileptogenic regions and thalamus evenly. ⢠Levetiracetam effect seen predominantly in cortices. ⢠Valproic acid has a cumulative effect on inhibiting brain activity in epileptogenic regions.
Asunto(s)
Anticonvulsivantes/farmacología , Encéfalo/efectos de los fármacos , Epilepsia/fisiopatología , Piracetam/análogos & derivados , Ácido Valproico/farmacología , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/uso terapéutico , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Niño , Relación Dosis-Respuesta a Droga , Electroencefalografía , Epilepsia/tratamiento farmacológico , Femenino , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/fisiopatología , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Levetiracetam , Imagen por Resonancia Magnética/métodos , Masculino , Piracetam/administración & dosificación , Piracetam/farmacología , Piracetam/uso terapéutico , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/efectos de los fármacos , Lóbulo Temporal/fisiopatología , Tálamo/diagnóstico por imagen , Tálamo/efectos de los fármacos , Tálamo/fisiopatología , Ácido Valproico/administración & dosificación , Ácido Valproico/uso terapéuticoRESUMEN
Juvenile hormone (JH) diol kinase (JHDK) is an important enzyme involved in the JH degradation pathway. Bombyx mori (Bommo)-JHDK cDNA (637bp) contains an open reading frame encoding a 183-amino acid protein, which reveals a high degree of identity to the two previously reported JHDKs. JHDK is similar to GTP-binding proteins with three conserved sequence elements involved in purine nucleotide binding, contains eight alpha-helices and three EF-hand motifs, and resembles the three-dimensional model of 2SCP and some other calcium-binding proteins. The Bommo-JHDK gene has only a single copy in the silkworm haploid genome, contains only one exon, and its 5'-upstream sequence does not have a JH response element. Although Bommo-JHDK is highly expressed in the gut of the silkworm, its mRNA expression remains at a constant level during larval development suggesting this enzyme is constitutive and not regulated by JH, at least at the transcriptional level. Recombinant Bommo-JHDK catalyzed the conversion of 10S-JH diol into JH diol phosphate, confirming its enzymatic function. Recombinant enzyme formed a dimer and had biochemical characteristics similar to other JHDKs. Bommo-JHDK, a calcium-binding protein with kinase activity, provides unique insights on how JH levels are regulated in the silkworm.