title: Decreased seizure activity in a human neonate treated with bumetanide, an inhibitor of the Na(+)-K(+)-2Cl(-) cotransporter NKCC1.
abstract: Neonatal seizures have devastating consequences for brain development and are inadequately treated by available antiepileptics. In neonates, gamma-aminobutyric acid (GABA) is an excitatory neurotransmitter due to elevated levels of intraneuronal chloride achieved by robust activity of the Na(+)-K(+)-2Cl( -) cotransporter (NKCC1). This depolarizing action of GABA likely contributes to the lowered seizure threshold, increased seizure propensity, and poor efficacy of GABAergic anticonvulsants among infants. The diuretic bumetanide inhibits NKCC1 and silences seizure activity in rodent models of neonatal seizures, but its effect on seizures in human neonates is unknown. Continuous electroencephalography (EEG) monitoring was used to quantify the number, duration, and frequency of seizures 2 hours before and after the administration of bumetanide in a neonate with intractable multifocal seizures. Significant reductions in mean seizure duration and frequency were noted following treatment, with no associated clinical side effects or metabolic imbalances. These results suggest bumetanide may exert antiepileptic effects in human neonates.
authors.affiliation: Department of Neurosurgery, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors.forename: Kristopher T
authors.initials: KT
authors.lastname: Kahle
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Barnett
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Sassower
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Staley
mesh_terms: D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002034:Bumetanide / Q000627:therapeutic use*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007223:Infant; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000627:therapeutic use*; D064506:Solute Carrier Family 12, Member 2; D013997:Time Factors
chemical_list: C578877:SLC12A2 protein, human; D049994:Sodium Potassium Chloride Symporter Inhibitors; D064506:Solute Carrier Family 12, Member 2; D002034:Bumetanide