Role of P-glycoprotein in refractoriness of seizures to antiepileptic drugs in Lennox-Gastaut syndrome.
Mechanism of seizure refractoriness to antiepileptic drugs in children with Lennox-Gastaut syndrome is not known. Efflux of antiepileptic drugs due to increased expression/function of P-glycoprotein, a multidrug efflux transporter protein on the cell surface is a proposed mechanism. The authors studied the expression/function of P-glycoprotein on peripheral blood mononuclear cells of 29 children with Lennox-Gastaut syndrome, 23 children with other epilepsies, and 19 healthy children. The authors found a higher P-glycoprotein expression/function in Lennox-Gastaut syndrome, a higher percent positive cells as compared to children with other epilepsy (P < 0.001) and to healthy controls (P = 0.012), higher P-glycoprotein expression as compared to healthy controls (P = 0.003), a higher total P-glycoprotein expression (relative florescence intensity × percent positive cells) as compared to children with other epilepsies (P < 0.001) and healthy controls (P < 0.001), and a higher P-glycoprotein function as compared to children with other epilepsies (P = 0.001) and healthy controls (P = 0.002). These findings may explain seizure refractoriness to anti-epileptic drugs in Lennox-Gastaut syndome.
Department of Neurology, SGPGIMS, Lucknow, Uttar Pradesh, India.
Achal
A
Kumar
Department of Clinical Immunology, SGPGIMS, Lucknow, Uttar Pradesh, India.
Deepak
D
Tripathi
Department of Neurology, SGPGIMS, Lucknow, Uttar Pradesh, India dr_vimalkpaliwal@rediffmail.com.
Vimal Kumar
VK
Paliwal
Department of Radiodiagnosis, SGPGIMS, Lucknow, Uttar Pradesh, India.
Zafar
Z
Neyaz
Department of Clinical Immunology, SGPGIMS, Lucknow, Uttar Pradesh, India.
Vikas
V
Agarwal
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000293:Adolescent; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006801:Humans; D065768:Lennox Gastaut Syndrome / Q000097:blood* / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018709:Statistics, Nonparametric; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D014700:Verapamil
Lennox-Gastaut syndrome; P-glycoprotein; multidrug resistance gene; refractory epilepsy