The Effect of Vagus Nerve Stimulation on Epileptiform Activity Recorded from Hippocampal Depth Electrodes

Abstract

Summary: Purpose:To assess the effect of vagus nerve stimulation (VNS) on interictal epileptiform activity in the human hippocampus. Clinical studies have established the efficacy of vagus nerve stimulation in patients with epilepsy (VNS Study Group, 1995), although the electrophysiologic effects of VNS on the human hippocampus and mesial temporal lobe structures remain unknown.Methods: We report a case study in which a patient with an implanted VNS underwent intracranial electrode recording before temporal lobectomy for intractable complex partial seizures. Epileptiform spikes and sharp waves were recorded from a depth electrode placed in the patient's left hippocampus. Spike frequencies and sharp-wave frequencies before and during VNS were compared using both a 5-and a 30-Hz stimulus. Different stimulation rates were tested on different days, and all analyses were performed using a Student's t test.Results: We found no significant differences in spike frequency between baseline periods and stimulation at 5 and 30 Hz. In contrast, stimulation at 30 Hz produced a significant decrease in the occurrence of epileptiform sharp waves compared with the baseline, whereas stimulation at 5 Hz was associated with a significant increase in the occurrence of epileptiform sharp waves.Conclusions: VNS produces a measurable electrophysiologic effect on epileptiform activity in the human hippocampus. Although a clinical response to VNS did not occur in our patient before surgery, 30-Hz VNS suppressed interictal epileptiform sharp waves that were similar in appearance to those seen during the patient's actual seizures. In contrast, 5-Hz stimulation appeared to increase the appearance of interictal sharp waves. Key Words: Vagus nerve stimulationHippocampal depth electrodes-Epileptiform activitySpikes-Sharp waves.Vagus nerve stimulation (VNS) using the NeuroCybernetic Prosthesis (NCP; Cyberonics, Inc., Houston, TX, U.S.A.) was approved by the Food and Drug Administration (FDA) in July 1997 for use as an adjunctive therapy for adults or adolescents older than 12 years with medically refractory partial onset seizures. Although its efficacy is well established (1,2), the exact mechanism of action of VNS remains unknown. Animal studies have shown that stimulation of the cervical portion of the vagus nerve can terminate electrographic seizures caused by either topical cortical or systemic strychnine or pentylenetetrazol (PTZ) (3). VNS can also block the development of kindled seizures (4).McLachlan (5) found that electrical stimulation of the left vagus nerve reduced or abolished penicillin-induced interictal cortical spikes in Wistar rats during and immediately after stimulation. In his study, stimulation consisted of square-wave pulses of 0.01-1.2 mA at 20 or 50 Hz. Woodbury and Woodbury (6) studied the effects of different stimulus parameters and found that stimulation of unmyelinated (C) vagus nerve fibers in male SpragueDawley rats could inhibit electrically or chemically induced seizures. They concluded that the optimal stimulus ...

Increase in 20–50Hz (gamma frequencies) power spectrum and synchronization after chronic vagal nerve stimulation

“…The performance of standard EEG, recorded for only 40 min in the present study,was not optimally suited to detect significant variations in spiking activity. However, previous studies with longer periods of EEG monitoring have shown that long-term VNS induces a delay in interspiking activity and a reduction in the frequency of epileptic interictal spikes (Koo, 2001;Kuba et al, 2002;Olejniczak et al, 2001), though a recent study which evaluated in children whether spike rates are useful as an outcome parameter following VNS yielded contrasting results (Ebus et al, 2004).…”

Beneficial effects on sleep of vagus nerve stimulation in children with therapy resistant epilepsy

“…Over the last years VNS has been shown in several animal studies, and recently in some human studies to suppress both ictal and interictal epileptiform EEG activity. [10][11][12][13][14] In an earlier report we present the findings that VNS reduces interictal epileptiform discharges in Rapid eye movement (REM) and slow wave sleep (SWS), and the number of electrographic seizures. 15 The effects of VNS on sleep in patients with medically refractory epilepsy have only been elucidated in a few studies and so far not in children.…”

Estimulación eléctrica vagal en el tratamiento de la epilepsia rebelde: Situación actual

“…Algunos estudios refieren cambios en la frecuencia de base en el EEG, dependiendo de la intensidad de la estimulación. Utilizando electrodos intracraneales se han encontrado cambios en la frecuencia de las descargas epileptiformes 55 . Otros estudios, sin embargo, no han confirmado cambios en el EEG, ni a simple vista ni en el análisis de frecuencias 23,45,66 .…”