Steven A. Reid

Efficacy and Safety of Vagus Nerve Stimulation in Patients With Complex Partial Seizures

Summary: A clinical trial of chronic intermittent vagal stimulation in five patients suggests that the procedure may be safe and effective as adjunctive treatment of medically intractable seizures of partial onset. Patients tolerated well the implantation of the neurocybernetic prosthesis and the vagal stimulation without serious physiological or lifestyle changes. Stimulation of the vagus nerve either reduced the seizure frequency or decreased the duration or intensity of seizures. Adverse side effects were limited to a tingling sensation in the throat and hoarseness during stimulation. A major complication was mechanical interruption of the wire‐electrode circuitry, with consequent cessation of stimulation. The small number of patients and the relatively short follow‐up period make this a pilot study, but the results are promising.

Electrophysiological Studies of Cervical Vagus Nerve Stimulation in Humans: I. EEG Effects

Summary: Evidence from studies of experimental animals indicates that electrical stimulation of the vagus nerve alters EEGs under certain stimulus parameters. We report EEG effects of electrical stimulation of the vagus nerve in 9 patients with medically intractable seizures as part of a clinical trial of chronic vagal stimulation for control of epilepsy. The mechanism of action of the vagal antiepileptic effect is unknown, and we believed that analysis of electrophysiologic effects of vagal nerve stimulation would help elucidate the brain areas affected. The left vagus nerve in the neck was stimulated with a programmable implanted stimulator. Stimulation at various stimulus frequencies and amplitudes had no noticeable effect on EEG activity whether the patient was under general anesthesia, awake, or asleep, but vagus nerve stimulation may interrupt ongoing ictal EEG activity.

Vagus Nerve Stimulation in Humans: Neurophysiological Studies and Electrophysiological Monitoring

Summary: Evidence from studies of experimental animals indicates that electrical stimulation of the vagus nerve alters behavioral and electrographic seizure activity. We report on effects of electrical stimulation of the vagus nerve in five patients with medically intractable seizures as part of a clinical trial of chronic vagal stimulation for control of epilepsy. The mechanism of action of the vagal antiepileptic effect is unknown, and it is hoped that analysis of electrophysiological effects of vagal nerve stimulation will help elucidate which brain areas are affected. Stimulation of the left vagus nerve in the neck was accomplished with a programmable implanted stimulator. Effects of stimulus amplitude, duration, and rate were studied. Noncephalic reference recording of the vagus‐nerve‐evoked potential showed some unusual properties: a scalp negative component occurred with latency of 12 ms, very high amplitude (up to 60 μV), and widespread scalp distribution. Field distribution studies indicate that this potential is generated in the neck, in the region of the stimulating electrodes. Muscle paralysis confirms this observation. Stimulation at various frequencies had no noticeable effect on electroencephalographic (EEG) activity regardless of whether the patient was under general anesthesia, awake, or asleep.

Electrophysiologic studies of cervical vagus nerve stimulation in humans. II: Evoked potentials

Summary: Evidence from studies of experimental animals indicates that electrical stimulation of the vagus nerve not only can alter the EEG but evokes activity in specific brain areas. We report effects of electrical stimulation of the vagus nerve in 9 patients with medically intractable seizures as part of a clinical trial of chronic vagal stimulation for control of epilepsy. The left vagus nerve in the neck was stimulated with a programmable implanted stimulator. Effects of stimulus amplitude, duration, and rate were studied. Noncephalic reference recording of the vagus nerve evoked potential showed some unusual properties: a scalp negative component occurred with a latency of 12 ms, very high amplitude (60 μV), and widespread scalp distribution. Field distribution studies indicated that this potential was myogenic in origin and generated in the region of the stimulating electrodes in the neck area. Chemically induced muscle paralysis confirmed this observation. Bipolar scalp recording showed several small‐amplitude topographically distinct potentials occurring in 30 ms. No effect, either acute or chronic, could be detected on pattern‐reversal evoked potentials, auditory brainstem evoked potentials, auditory 40‐Hz potentials, or cognitive evoked potentials.

Histopathology of the ferric-induced chronic epileptic focus in cat: A Golgi study

Abstract Five cats were rendered chronically epileptic via subpial injection of saturated FeCl 3 solution. Six weeks postinjection, electrocorticographic recording demonstrated focal epileptiform spiking in the region of the injection. This finding was not observed in saline-injected controls. Histopathological analysis of the epileptic focus using Nissl and Golgi-Cox techniques revealed (i) depopulation of Golgi-impregnated neurons, (ii) astocytic gliosis, (iii) loss of dendritic spines, (iv) decreased dendritic branching, and (v) dendritic varicosities. These are similar to the pathological findings which have been described for human epileptogenic foci. These results, in combination with the frequent observation of hemosiderosis in regions of human epileptogenic foci, implicate the release of iron from extravasated blood elements as a possible etiologic mechanism. Therefore, we believe the FeCl 3 experimental epileptogenic focus accurately models the human clinical entity (posttraumatic epilepsy) with respect to both electrophysiology and histopathology.

Outcome for West Syndrome Following Surgical Treatment

Summary: We report the case of an 18‐month‐old child with infantile spasms and a hypsarrhythmic electroencephalogram (EEG) pattern associated with a porencephalic cyst. Surgical removal of the cyst and its surrounding tissue was performed following failure of medical therapy. Postoperatively, the patient has béen frée of infantile spasms for 12 months and the EEG has normalized. He has béen maintained on the same preoperative antiepileptic medications. This case suggests that surgical treatment is helpful in selected patients with infantile spasms and focal CNS lesions.

Absence of cortical white matter changes in three patients undergoing long-term vigabatrin therapy

Chronic administration of the experimental antiepileptic drug vigabatrin (gamma-vinyl GABA) to animals has been shown to cause dose-dependent neuropathological changes characterized by a microvacuolation in specific white matter tracts. This finding has led to some concern as to whether similar pathologic changes might occur in patients taking this medication. Here we report on analysis of tissue specimens taken during neurosurgery from three patients undergoing chronic vigabatrin therapy (4 g/day). The first patient, a 34-year-old woman, had taken vigabatrin for 2 years prior to surgery, the second, a 50-year-old man, had taken the drug for 1 year, and a 34-year-old man had taken the drug for 5.3 years. For comparison, similar specimens were taken from three other patients not taking vigabatrin who were undergoing surgery for intractable epilepsy. Specimens from each subject were prepared in an identical manner and examined with light and electron microscopy. All specimens were examined in a blinded fashion. There was some minor nonspecific myelinic splitting seen in both controls and vigabatrin-treated patients but there was no evidence for any drug-induced lesions similar to that seen in experimental animals.

STL: A Spatio-Temporal Characterization of Focal Interictal Events

SummaryAn innovative method for on-line processing of array ECoG data, the Spatio-Temporal Laplacian, intended for intraoperative epileptic focus localization is presented. This method simultaneously involves the spatial and temporal characteristics of the potential field manifestations peculiar to focal interictal events. A 3-Dimensional (x, y and t) sample space is used to explain and apply the Spatio-Temporal Laplacian (STL) transformation. In particular, a focal interictal event is detected through the coincident spatial and temporal sharpness that it introduces in this sample space. Preliminary results from two subjects are presented and compared with standard bipolar derivation signals, traditionally used in the focus localization task.

Intraoperative focus localization system based on spatio-temporal ECoG analysis

Surgical therapy has been shown to provide significant relief io a number of eligible patients with othenvise intractable focal epilepsy. In the interest of these patients, the neurosurgeon may try to “tailor” the resection of cerebral cortex according to intraoperative findings regarding the location of the epileptic focus. This enhanced focus localization is achieved by reading the electrocorticogram (ECoG) obtiined from an may of electrodes (Fig. l ) , placed directly on the exposed cerebral cortex of the subject, prior to the resection. The system described here has been designed as a tool to facilitate the localization of the epiIeptic focus using the signals obtained from the ECoG array.

Multidimensional filtering of the electrocorticogram (ECoG) for epileptic focus localization

The rationale of a method for the detection and localization of focal epileptic activity from multichannel ECoG recordings is introduced. The proposed method, the spatiotemporal Laplacian, emphasizes the need to consider both the spatial and the temporal attributes of focal epileptic activity. In its current implementation the method discriminates the events of interest by means of combined measures of spatial and temporal sharpness, yielding a two-dimensional representation that facilitates the localization of the focus. Some preliminary offline results are presented.<<ETX>>