Electroencephalography (EEG) and Deep Brain Stimulation (DBS) in Epilepsy
Electroencephalography (EEG) and Deep Brain Stimulation (DBS) in Epilepsy
Patients with epilepsy undergoing deep brain stimulation (DBS) have electroencephalograms
 (EEGs) recorded before and during their stimulation treatment. Subsequently the investigators
 will be using computer-assisted analysis of the digitally-recorded EEG signals to assess the
 effects of DBS on the brain-wave frequency content and any abnormal seizure-like patterns
 that may be present.
Study Purpose:

 The purpose of this study is to assess EEG changes during electrical stimulation of the
 thalamus to treat people with epilepsy.

 Background on stimulation of the anterior nucleus of the thalamus for epilepsy:

 Of the estimated 4 million people in the U.S. and Europe with epilepsy, approximately 1.2
 million have recurrent seizures that do not respond to antiepileptic drugs. For these
 patients, alternative treatments consist of neurosurgical removal of the seizure source from
 the brain, or surgical implantation of a device to electrically stimulate the vagus nerve in
 the neck. In spite of these options, a significant number of people suffer from seizures that
 remain uncontrolled. For this group, deep brain stimulation (DBS) may be helpful.

 The rationale for using deep brain stimulation (DBS) to treat epilepsy is that DBS disrupts
 regulatory feedback loops in the brain that allow seizures to develop and spread. By
 influencing these regulatory areas in the brain, electrical stimulation has the capacity to
 reduce or eliminate seizures that originate in portions of the brain that cannot safely be
 surgically removed. Vagus nerve stimulation (VNS) works in a similar way against seizures,
 but VNS disrupts the regulatory loops indirectly, while DBS disrupts the regulatory loops
 directly.

 The thalamus is an appealing target for DBS to treat epilepsy because it has widespread
 connections to, and influences on, the cerebral cortex, which is the outer layer of the brain
 where seizures originate. Fourteen patients with various types of refractory epilepsy have
 been treated with stimulation of the anterior nucleus (AN) of the thalamus during the past
 several years. During the first 3 months of AN stimulation, the median seizure frequency
 reduction, relative to baseline, was 64%. Eight of the 14 patients (57%) had a 50% or greater
 decrease in seizure frequency (responders). Nine of the 14 patients had seizures presumed to
 arise from the temporal or frontal lobes. During the first 3 months, these 9 patients had a
 median 80% reduction in seizure frequency and 78% of them were responders. The AN was
 selected for stimulation because of its many connections to the "limbic system", a cortical
 system which is often a source of seizures.

 Prior studies of thalamic stimulation for epilepsy (centromedian nucleus [CM]) The majority
 of the research addressing stimulation of the thalamic centromedian nucleus (CM) for the
 treatment of epilepsy has been reported by Velasco et al. (1-3). In 1987, the group published
 a paper in which 5 patients with generalized tonic-clonic seizures were implanted
 bilaterally. Stimulation was delivered 2 hours per day for 3 months. All patients experienced
 an 80-100% reduction in generalized tonic-clonic seizures and a 60-100% reduction in partial
 complex seizures. Much of the benefit observed continued beyond the 2-hour period of
 stimulation, suggesting that the stimulation resulted in a long-term change in thalamic
 activity.

 In 1993, the same group published a report of 23 patients with externalized CM
 stimulators(2,3) (9 with generalized tonic-clonic seizures, 3 with focal motor and secondary
 generalized seizures, 5 with partial complex and secondary generalized seizures, and 6 with
 generalized tonic seizures and atypical absence seizures). These investigators found that
 stimulation resulted in a significant decrease in seizure frequency in the patients with
 tonic-clonic and partial motor seizures. However, no significant changes were observed in
 patients with complex partial seizures or generalized tonic seizures. Overall, 12 of the 23
 patients had at least a 50% decrease in seizure frequency, and 1 patient was seizure free.

 None of these studies from the Mexico City group (Velasco et al.) were blinded or controlled.
 However, in 1992, Fisher et al. (4) from John Hopkins reported a double-blind, controlled
 trial of CM stimulation. This treatment had no effects on the patients. Therefore, CM
 stimulation was abandoned and AN stimulation was undertaken instead.

 Electroencephalograms (EEG) and thalamic stimulation for epilepsy An electroencephalogram
 (EEG) is a recording of brain wave electrical activity. The cerebral cortex nerve cells
 generate the EEG signal. The principal features of the EEG studied in patients with epilepsy
 are: 1) how rapidly and often the electrical signal changes amplitude ("frequency"), and 2)
 any abnormal excessive very brief unexpected electrical discharge ("spike-waves").
 Spike-waves are the type discharges characteristic of patients with epilepsy.

 Electrical stimulation of the CM nucleus of the thalamus has resulted in less EEG spike-waves
 (1-3). However, there have been no studies of EEG frequency in epilepsy patients receiving AN
 stimulation therapy.

 For this study the investigators will record EEGs on computerized monitors. These recording
 machines are small portable computers (about the size of a "Walk-Man") which the patient
 wears for one hour. The brain-wave sensing electrodes are attached to the patients' scalp
 with a water-soluble temporary conducting glue. These monitors are placed on the patients in
 the EEG laboratory at New York Hospital-Cornell. The recorded EEG signal is downloaded to our
 EEG analysis computer. This is a routine test commonly performed to evaluate patients with
 epilepsy, and the ambulatory EEG in and of itself is not experimental in any way.

 EEGs will be recorded at the following times relative to the DBS treatment for epilepsy: 1
 month before stimulator implant, 1 month after stimulator implant (but before stimulator
 activation), after 3 months of DBS, after 6 months of DBS, and thereafter every 6 months or
 after stimulation setting changes.

 The recorded EEGs will be mathematically analyzed, according to the following line of
 reasoning: Nerve cells in the thalamic AN connect to the cerebral cortex. AN activity (and AN
 stimulation) therefore may change how rapidly the electrical potentials of the cortex nerve
 cells change, which in turn may change the EEG frequency content. The investigators will
 utilize computer programs to determine the EEG frequency content, using a tool called
 "spectral analysis". The investigators will compare the spectral analysis between different
 time periods during the DBS treatment regimen.

 Another feature the investigators will study is "EEG coherence". This is a computer-generated
 measure of how similar the brain wave frequencies are in different brain cortex regions.
 Since AN nerve cell activity regulates cortex nerve cell activity, AN stimulation may cause
 cortical activity in different regions of the brain to be more similar to each other. This
 type of change in cortical activity might be part of the mechanism of action of DBS against
 epilepsy. The investigators will compare the coherence analysis between different times
 during the DBS treatment regimen.
Inclusion Criteria:

 -  To be scheduled to undergo deep brain stimulation therapy (DBS) in an attempt to treat
 intractable epilepsy

 Exclusion Criteria:

 -  None