Previously reported probands with de novo missense mutations in DNM1L presented in the first year of life with severe encephalopathy and refractory epilepsy, with several dying within the first several weeks after birth.
Previously reported probands with de novo missense mutations in DNM1L presented in the first year of life with severe encephalopathy and refractory epilepsy, with several dying within the first several weeks after birth.
Identification of a somatic mutation in the RHEB gene through high depth and ultra-high depth next generation sequencing in a patient with Hemimegalencephaly and drug resistant Epilepsy.
CDKL5 deficiency is caused by mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene and clinically manifests often in females as drug-resistant intractable epilepsy and severe psychomotor retardation.
Taking together, these data suggest that stimulation of EPO depending signaling system could not only play a central role in brain cell protection, but this system could be a new tool for reverse the pharmacoresistant phenotype in refractory epilepsy as well as in other pharmacoresistant hypoxic brain diseases expressing P-gp.
These data suggested that overexpression of P-gp and CYP3A during seizures and treated with CBZ may be regulated by PXR or NF-κB p65 activity and expression, which revealed a mechanism underlying the development of DRE.
Neuroinflammation due to high levels of glutamate has been identified as one of the causes of P-gp upregulation, and several studies in animal models of epilepsy suggest that antiinflammatory drugs might prevent P-gp overexpression and, thus, avoid the development of refractory epilepsy.
Consequently, RE and SUDEP share a multidrug resistance (MDR) phenotype, which is mainly associated with brain overexpression of ABC-transporters such as P-glycoprotein (P-gp).
We aimed to investigate the expression levels of multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein 1 (MRP1) and multidrug resistance P-glycoprotein (P-gp) in peripheral blood of patients with refractory epilepsy.
We aimed to investigate the expression levels of multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein 1 (MRP1) and multidrug resistance P-glycoprotein (P-gp) in peripheral blood of patients with refractory epilepsy.
Mutations in the CDKL5 (cyclin-dependent kinase-like-5) gene are known to determine early-onset drug resistant epilepsies and severe cognitive impairment with absent language, hand stereotypies, and deceleration of head growth.
The overexpression of multidrug transporters, as the P-glycoprotein (P-gp), at the level of the blood-brain barrier of epileptic patients has been suggested as a key mechanism underlying the refractory epilepsy.
Thus, our findings suggest that miR-298 reverses MDR to AEDs by inhibiting P-gp expression, suggesting a potential target for overcoming MDR in refractory epilepsy.
The results revealed that LTG-loaded mPEG-PLA/TPGS mixed micelles enhanced the absorption of LTG at the nasal cavity and reduced the efflux of LTG in the brain, suggesting that the function of TPGS inhibited P-glycoprotein and LTG-loaded mPEG-PLA/TPGS mixed micelles had the potential to overcome refractory epilepsy.