title: Combined ketogenic diet and vagus nerve stimulation: rational polytherapy?
abstract: OBJECTIVE
  The concept of "rational polypharmacy" has been associated with anticonvulsant management for decades, but the term has not been applied to nonpharmacologic therapies.
  
  
  METHODS
  We conducted a multicenter, retrospective study of children who received concurrent diet (ketogenic or modified Atkins) and vagus nerve stimulation (VNS) treatment for medically intractable epilepsy.
  
  
  RESULTS
  Thirty children in total from six epilepsy centers were treated over a 6-yr period. The median age at the initiation of combination therapy was 10 yr (range, 4-24 yr). Sixteen (53%) received dietary therapy followed by VNS; no differences were noted between centers. After 3 months, 21 (70%) had seizure reduced by >50% over the previous single nonpharmacologic treatment, of whom 13 (62%) had improvement within the first month. A 5-min VNS off-time correlated with >90% seizure reduction (p = 0.02). The median duration of nonpharmacologic polytherapy was 12 months (range, 0.5-96 months); 17 (57%) remain on dual therapy at this time. No side effects were noted. Most patients who discontinued combination therapy did so because of a lack of efficacy rather than restrictiveness.
  
  
  CONCLUSIONS
  In this small group, the combined use of diet and VNS appeared synergistic and yielded rapid benefits. It may be more effective with longer VNS off-times. Further prospective studies of this combination in refractory pediatric epilepsy are needed to help guide optimal use.
authors.affiliation: The Johns Hopkins Hospital, Baltimore, Maryland 21287-1000, USA. ekossoff@jhmi.edu
authors.forename: Eric H
authors.initials: EH
authors.lastname: Kossoff
authors.forename: Paula L
authors.initials: PL
authors.lastname: Pyzik
authors.forename: James E
authors.initials: JE
authors.lastname: Rubenstein
authors.forename: A G Christina
authors.initials: AG
authors.lastname: Bergqvist
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Buchhalter
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Donner
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Nordli
authors.forename: James W
authors.initials: JW
authors.lastname: Wheless
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D050528:Diet, Carbohydrate-Restricted; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism*; D004599:Electric Stimulation Therapy / Q000379:methods*; D004827:Epilepsy / Q000178:diet therapy* / Q000378:metabolism / Q000628:therapy*; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007662:Ketosis / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D012189:Retrospective Studies; D016896:Treatment Outcome; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D004041:Dietary Fats