VNS and EEG
ABSTRACT & COMMENTARY
Source: Schachter SC, Saper CB. Vagus nerve stimulation. Epilepsia 1998;39:677-686.
Schachter and saper, in their useful review, report that electrical stimulation of the left vagal nerve (VNS) has long been known to slow EEG patterns. Zanchetti and colleagues reported the phenomenon in cats.1 Relatively slow progress marked its relationship to human epilepsy until the late Kitten, Penry, and Dean emphasized its capacity to block intractable partial seizures in humans.2 Wilder and Uthman reported additional successful studies in 1991 and 1993, respectively.3,4 A larger group of 114 patients (EO3 study) was directed mainly at victims of partial seizures. At the same time, a group of patients was selected for a compassionate use trial. A final pre-FDA clearance trial (EO5) was completed in 1997 and carefully evaluated and reported by Handforth.5
Schachter and Saper indicate that both EO3 and EO5 study groups found that high-stimulation protocols appeared to be more successful than low-stimulation patterns. Inclusion requirements for persons in the EO3 study consisted of the following: at least six seizures monthly, no more than 14 consecutive non-seizure days, older than 12 years, predominantly partial seizures, and consistent baseline treatment using standard anti-epileptic drugs (AEDs). Excluded were progressive or unstable illnesses, pregnancy, and the immediate use of an investigational AED. The EO5 protocol was similar to the EO3 but accepted three weeks between seizures, admission of 12- to 65-year-olds, and the use of an acceptable anti-fertility drug. Factors vetoing participation included progressive neurological disease, active cardiopulmonary disease, peptic ulcer, prior vagotomy, status epilepticus in the past 16 months, or past epilepsy surgery.
One hundred fourteen patients participated in the EO3 study and underwent implantation of the neurocybernetic prosthesis (NCP) on the left vagal nerve in the neck. The EO5 group contained 196 patients. Outcome analysis included changes in total seizure frequency from baseline, comparing high and low stimulation intensity. Mean decrease of seizure frequency in the EO3 was 24.5% among high stimulation recipients compared to 6.1% following low stimulation (P = 0.01). EO5 results indicated a 28% decrease of seizures in high frequency recipients vs. 15% among the low frequency group (P = 0.039). In more limited ways, 31% of the EO3 high stimulation group had at least a 50% reduction of seizures compared to 13% in those who received low stimulation. The EO5 group showed similar extreme responses: 11% of the high stimulated patients reduced their seizures more than 75%, compared to the 2% in the low stimulation cohort (P = 0.01).
Only limited reports have dealt with the efficacy of VNS in children. Murphy and associates described 12 children, aged 4-16 years old, with refractory epilepsy receiving the treatment.6 Three had more than 90% reduction in seizure frequency, and four others were measurably improved. Lundgren now describes 16 youngsters aged 4-19 years: eight had partial, and the others suffered generalized attacks prior to the vagal nerve implant.7 Four of the latter had Lenox-Gastaut syndrome. Of the 16, seven had undergone previous epilepsy surgery, and nine had been refused such a step. Six of the children enjoyed 50% or greater frequency when evaluated 10-12 months after implantation, and a somewhat different group of six children experienced improved quality of life. Stimulation produced no beneficial effect in five children and was discontinued.
COMMENTARY
It appears that VNS may join epilepsy surgery in measurably reducing seizures in patients who consistently resist present pharmacological control. No serious complications have arisen, although modest post-operative pain, hoarseness, altered voice sounds, coughing, dyspnea, and voice alteration were singly or more encountered in 15% of total subjects. Neither wound infections nor an increase of seizures has been reported. But, reported results on VNS remain small, and current information is said to include only 2000 life-years of patient exposure. Hopefully, technical improvements may reduce unwanted side effects, and selective anti-epileptic drugs may be developed to amplify the efficiency of the stimulators. -fp
References
1. Zanchetti, et al. Electroencephalogr Clin Neurophysiol 1952;4:359-361.
2. Penry JK, Dean JC. Prevention of intractable partial seizures by intermittent vagal stimulation in humans: Preliminary results. Epilepsia 1990;31:S40-S43.
3. Wilder BJ, et al. Vagal stimulation for control of complex partial seizures in medically refractory epileptic patients. Pacing Clin Electrophysiol 1991;14:108-115.
4. Uthman BM, et al. Treatment of epilepsy by stimulation of the vagus nerve. Neurology 1993;43:1338-1345.
5. Handforth A, et al. Vagus nerve stimulation therapy for partial-onset seizures: A randomized active-control trial. Neurology 1998;51:48-55.
6. Murphy JV, et al. Left vagal nerve stimulation in children with refractory epilepsy. Preliminary observations. Arch Neurol 1995;52:886-889.
7. Lundgren J, et al. Vagus nerve stimulation in 16 children with refractory epilepsy. Epilepsia 1998; 39:809-813.
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