Short term benefit of battery depletion in vagus nerve stimulation for epilepsy
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《神经病学神经外科学杂志》
Krembil Neuroscience Centre, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, 5W444, Toronto, ON Canada M5T 2S8; r.wennberg@utoronto.ca
Keywords: epilepsy; neurostimulation; vagus nerve stimulation
Interest in neurostimulation to treat epilepsy has rekindled over the past decade, with vagus nerve stimulation (VNS) now an
If stimulation of the vagus nerve is actually a necessary part of VNS for epilepsy, depletion of the stimulator battery would be expected to result in an increase in seizures. Indeed, status epilepticus was recently reported to have occurred in one patient after stopping VNS for an elective brain MRI scan.4
No study has been formally published describing the effects of battery depletion in a large group of patients treated with VNS for epilepsy, however, the data from just such a study have been published informally—in the Cyberonics VNS Physician’s Manual.5 It is of interest to examine these data. Over the course of follow up of patients in the E03 VNS trial,6 a total of 72 battery depletions in 68 patients occurred. Seizure frequency after battery depletion was monitored for one to four weeks after stimulation was stopped, with the outcome results divided into three groups: patients having a greater than 25% increase in seizures, patients unchanged with a less than 25% increase or decrease in seizures, and patients with a greater than 25% decrease in seizures. Forty two of 72 cases (58%) were in the last group—that is, the large majority of patients improved after battery depletion. Nineteen of 72 cases (26%) were unchanged and 11 of 72 (15%) worsened.
A 2 analysis of the results comparing patients with a greater than 25% seizure reduction with patients with a greater than 25% increase in seizures after battery depletion shows a highly significant benefit to battery failure (p<0.0001; 2 = 18.14, two tailed test). This is the most significant finding of any statistical analysis performed in all of the VNS studies used to support licensing of the device as a treatment for epilepsy.5–7 As the research hypothesis here specifies the direction in which a change will occur—that is, "there will be an increase in seizures when VNS stops," the alternative hypothesis is actually one tailed, which makes the significance of the findings even greater (p<0.00005). This means that the probability that the observed findings of improvement with battery depletion in most patients could have occurred by chance is less than 1 in 20 000. It is possible that the findings do represent such a chance occurrence. It is equally possible, or perhaps more probable, that any sort of non-specific change in patients with epilepsy might provide a perturbation sufficient to effect improvements in seizure control, at least in the short term. Either way, benefits in seizure control with VNS in humans seem to have little specific to do with active stimulation of the vagus nerve.
References
Benbadis SR, Tatum IV WO, Vale FL. When drugs don’t work. An algorithmic approach to medically intractable epilepsy. Neurology 2000;55:1780–4.
McLachlan R. Suppression of interictal spikes and seizures by stimulation of the vagus nerve. Epilepsia 1993;34:918–23.
Hodaie M, Wennberg RA, Dostrovsky JO, et al. Chronic anterior thalamus stimulation for intractable epilepsy. Epilepsia 2002;43:603–8.
Beitinjaneh F, Guido M III, Andriola MR. Status epilepticus precipitated by turning off the vagus nerve stimulator for elective brain MRI. . Epilepsia 2002;43(suppl 7):337–8.
Cyberonics. Physician’s manual for the NeuroCybernetic prothesis system. NCP pulse generator. Houston: Cyberonics, 2000.
The Vagus Nerve Stimulation Study Group. A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. Neurology 1995;45:224–30.
Handforth A, DeGiorgio CM, Schachter SC, et al. Vagus nerve stimulation therapy for partial-onset seizures. A randomized active-control trial. Neurology 1998;51:48–55.(R Wennberg)
Keywords: epilepsy; neurostimulation; vagus nerve stimulation
Interest in neurostimulation to treat epilepsy has rekindled over the past decade, with vagus nerve stimulation (VNS) now an
If stimulation of the vagus nerve is actually a necessary part of VNS for epilepsy, depletion of the stimulator battery would be expected to result in an increase in seizures. Indeed, status epilepticus was recently reported to have occurred in one patient after stopping VNS for an elective brain MRI scan.4
No study has been formally published describing the effects of battery depletion in a large group of patients treated with VNS for epilepsy, however, the data from just such a study have been published informally—in the Cyberonics VNS Physician’s Manual.5 It is of interest to examine these data. Over the course of follow up of patients in the E03 VNS trial,6 a total of 72 battery depletions in 68 patients occurred. Seizure frequency after battery depletion was monitored for one to four weeks after stimulation was stopped, with the outcome results divided into three groups: patients having a greater than 25% increase in seizures, patients unchanged with a less than 25% increase or decrease in seizures, and patients with a greater than 25% decrease in seizures. Forty two of 72 cases (58%) were in the last group—that is, the large majority of patients improved after battery depletion. Nineteen of 72 cases (26%) were unchanged and 11 of 72 (15%) worsened.
A 2 analysis of the results comparing patients with a greater than 25% seizure reduction with patients with a greater than 25% increase in seizures after battery depletion shows a highly significant benefit to battery failure (p<0.0001; 2 = 18.14, two tailed test). This is the most significant finding of any statistical analysis performed in all of the VNS studies used to support licensing of the device as a treatment for epilepsy.5–7 As the research hypothesis here specifies the direction in which a change will occur—that is, "there will be an increase in seizures when VNS stops," the alternative hypothesis is actually one tailed, which makes the significance of the findings even greater (p<0.00005). This means that the probability that the observed findings of improvement with battery depletion in most patients could have occurred by chance is less than 1 in 20 000. It is possible that the findings do represent such a chance occurrence. It is equally possible, or perhaps more probable, that any sort of non-specific change in patients with epilepsy might provide a perturbation sufficient to effect improvements in seizure control, at least in the short term. Either way, benefits in seizure control with VNS in humans seem to have little specific to do with active stimulation of the vagus nerve.
References
Benbadis SR, Tatum IV WO, Vale FL. When drugs don’t work. An algorithmic approach to medically intractable epilepsy. Neurology 2000;55:1780–4.
McLachlan R. Suppression of interictal spikes and seizures by stimulation of the vagus nerve. Epilepsia 1993;34:918–23.
Hodaie M, Wennberg RA, Dostrovsky JO, et al. Chronic anterior thalamus stimulation for intractable epilepsy. Epilepsia 2002;43:603–8.
Beitinjaneh F, Guido M III, Andriola MR. Status epilepticus precipitated by turning off the vagus nerve stimulator for elective brain MRI. . Epilepsia 2002;43(suppl 7):337–8.
Cyberonics. Physician’s manual for the NeuroCybernetic prothesis system. NCP pulse generator. Houston: Cyberonics, 2000.
The Vagus Nerve Stimulation Study Group. A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. Neurology 1995;45:224–30.
Handforth A, DeGiorgio CM, Schachter SC, et al. Vagus nerve stimulation therapy for partial-onset seizures. A randomized active-control trial. Neurology 1998;51:48–55.(R Wennberg)