Combined ketogenic diet and vagus nerve stimulation: rational polytherapy?
Kossoff EH, Pyzik PL, Rubenstein JE, Bergqvist AG, Buchhalter JR, Donner EJ, Nordli DR Jr, Wheless JW.
Epilepsia. 2007 Jan;48(1):77-81.
https://doi.org/10.1111/j.1528-1167.2006.00903.x.
Continuing on the theme from last week, Kossoff et al. in 2007 investigated if a combination of vagus nerve stimulation (#VNS) therapy and ketogenic diet (#KD) could be a valuable approach for treating #children with drug resistant epilepsy (#DRE). In their #multicentre, #retrospective study, 30 patients from 6 different #pediatric centres in the USA were treated with a combination therapy of VNS and KD (or modified Atkins diet; #MAD) when one of the treatment modalities alone had not resulted in desirable seizure control.
Highlights:
• A combination therapy of VNS and KD/MAD may have #synergistic effects on seizure burden in pediatric patients with DRE.
• The choice of initial therapy (VNS or KD first) did not affect seizure response.
• A significant correlation was found between a >90% seizure reduction (on top of single therapy) and a 5 min OFF time, indicating a superior effect with longer VNS duty cycles. However, it should be noted that significantly more patients were on a regular duty cycle (30 s ON, 5 min OFF) compared to rapid cycling.
• The combination of VNS Therapy and KD/MAD were well tolerated with surprisingly no reported adverse events and 57% of the patients remained on polytherapy when the article was published.
In the current study, the patients were on single therapy for a median duration of 18 months and 24 months respectively for KD (zero patients had a single therapy with MAD) and VNS Therapy prior to polytherapy. The median age at the start of polytherapy was 9.5 years and the median duration of combination therapy was 12 months (0.5-96 months). 77% of the patients had a >50% seizure reduction with single therapy. However, after 3 months on the combination therapy, 70% of the patients had a >50% seizure reduction on top of the effect with single therapy. The corresponding value was 63% after 6 months, partly due to discontinuation of the combination therapy because of insufficient seizure reduction.
Both therapies were well tolerated, and no side effects were reported. However, the discontinuation of combination therapy, especially for the patients with large improvement in seizure burden, might be an indication of difficulties in combining the two treatment modalities.
In conclusion, the study suggests that a combination of VNS and KD to have a synergistic interaction which may reduce seizure burden in pediatric patients with DRE. However, further prospective studies are needed in order to fully evaluate the effectiveness of this nonpharmacological combination therapy.