The long-term effect of VNS on QoL in patients with pharmacoresistant focal epilepsy

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The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: The PuLsE (Open Prospective Randomized Long-term Effectiveness) trial.

Source: Epilepsia Early View, Article first published online: 22 APR 2014
Authors: Philippe Ryvlin, Frank G. Gilliam, Dang K. Nguyen, Gabriella Colicchio, Alfonso Iudice, Paolo Tinuper, Nelia Zamponi, Umberto Aguglia, Louis Wagner, Lorella Minotti, Hermann Stefan, Paul Boon, Mark Sadler, Paolo Benna, Pradheep Raman, and Emilio Perucca


To evaluate whether vagus nerve stimulation (VNS) as adjunct to best medical practice (VNS + BMP) is superior to BMP alone in improving long-term health-related quality of life (HRQoL).


PuLsE was a prospective, randomized, parallel-group, open label, and long term effectiveness study (conducted at 28 sites in Europe and Canada). Adults with pharmacoresistant focal seizures (n=112) received VNS + BMP (Best Medical Practice) or BMP (1:1 ratio). Medications and VNS parameters could be adjusted as clinically indicated for optimal seizure control while minimizing adverse effects. Primary endpoint was mean change from baseline HRQoL (using Quality of Life in Epilepsy Inventory-89 total score; QOLIE-89). Secondary endpoints included changes in seizure frequency, responder rate (≥50% decrease in seizure frequency), Centre for Epidemiologic Studies Depression scale (CES-D), Neurological Disorders Depression Inventory-Epilepsy scale (NDDI-E), Clinical Global Impression-Improvement scale (CGI-I), Adverse Event Profile (AEP), and antiepileptic drug load (AED).The study was prematurely terminated due to recruitment difficulties prior to completing the planned enrolment of n=362. Results for n=96, who had baseline and at least one follow-up QUOLIE-89 assessment (from months 3-12) were included in this analysis. Mixed model repeated measures (MMRM) analysis of variance was performed on change from baseline for the primary and secondary endpoints.


Significant between-group differences in favour of VNS+BMP were observed regarding improvement in HrQoL, seizure frequency, and CGI score (respective p-values < 0.05, 0.03 and 0.01).l More patients in the VNS+BMP group (43%) reported adverse events (AEs) versus BMP group (21%) (p=0.01), a difference reflecting primarily mostly transient AEs related to VNS implantation or stimulation. No significant difference between treatment groups was observed for changes in CES-D, NDDI-E, AEP, and AED load. Significance: VNS therapy as a treatment adjunct to BMP in patients with pharmacoresistant focal seizures was associated with a significant improvement in HrQoL, compared with BMP alone.

Comments reviewer, prof Van Nieuwenhuizen:

this is an important study based on data from a considerable number of centres (28). The starting-point – VNS+BMP versus BMP – is for clinicians extremely relevant because it reflects daily clinical practice (doing the best you can for the patient, not being tied to rigid protocols regarding AED dosage or VNS parameters). The study had to labour under recruitment difficulties. Low enrolment was caused by strong positive or negative views on VNS in most study candidates.
This patient attitude can also be found in AED studies. RCT (including sham operations or device switched off) design could not be considered for ethical reasons. Only 7 patients achieved 2 year follow-up. 96 patients (48 allocated to VNS+BMP and 48 to BMP) had baseline data and at least one post baseline follow-up. At termination of the study, sixty of the 96 patients had completed their one year follow up; 55 of the sixty patients had QuOLIE-89 data available at each visit (0,3,6,9,12 months). However, the final number of included patients allowed important messages based on adequate statistical analyses, improvement in HrQoL being the most striking whereas significant decrease of seizure frequency is obviously equally important for patients suffering of epilepsy. Adverse events were more frequently reported in the VNS+BMP group, related to implantation of the device and electrical stimulation within VNS scheme.

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