title: Addition of verapamil in the treatment of severe myoclonic epilepsy in infancy.
abstract: We report on the use of the voltage-gated calcium channel blocker (Vg-CCB), verapamil, as an add-on anticonvulsant medication in two girls, 4 and 14 years of age, who were affected by severe myoclonic epilepsy in infancy (SMEI) or Dravet syndrome, a channelopathy caused by abnormalities in the voltage-gated sodium channel neuronal type alpha1 subunit (SCN1A) gene at 2q24. Both girls had pharmacoresistant epilepsy and developmental delay. Mutation analysis for the SCN1A gene revealed a missense mutation in exon 2 in the 4-year-old girl. Verapamil was co-administered in both children with a prompt response in controlling status epilepticus, myoclonic jerks, and partial and generalized seizures. The therapeutic effect lasted 13 months in the 14-year-old girl, while it is still present after a 20-month follow-up period in the 4-year-old girl who, in addition, has experienced improvement in motor and language development. The verapamil vVg-CCB, which crosses the blood-brain barrier (BBB): (a) inhibits the P-glycoprotein, an active efflux transporter protein expressed in normal tissue, including the brain, which is believed to contribute to the in situ phenomenon of multidrug resistance; and (b) may regulate membrane depolarization induced by abnormal sodium channels functions by modulating the abnormal Ca++ influxes into neurons with subsequent cell resting. This is the first report on long-lasting verapamil therapy in SMEI. The functional consequences of such in vivo modulating effects on Ca++ channels could contribute to rational targeting for future molecular therapeutic approaches in pharmacoresistant epileptic channelopathies.
authors.affiliation: Division of Pediatric Neurology, Department of Paediatrics, University of Rome La Sapienza, Viale Regina Elena, 324, Roma 00161, Italy. paola.iannetti@uniroma1.it
authors.forename: Paola
authors.initials: P
authors.lastname: Iannetti
authors.forename: Pasquale
authors.initials: P
authors.lastname: Parisi
authors.forename: Alberto
authors.initials: A
authors.lastname: Spalice
authors.forename: Martino
authors.initials: M
authors.lastname: Ruggieri
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002675:Child, Preschool; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D004569:Electroencephalography / Q000379:methods; D004831:Epilepsies, Myoclonic / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics; D014700:Verapamil / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels; D014700:Verapamil