Mark D. Holmes MD
Professor, Department of Neurology
Regional Epilepsy Center
University of Washington, Seattle WA
The evaluation of a person with epilepsy requires a thorough assessment, including a detailed clinical examination, and use of several laboratory studies, especially brain magnetic resonance imaging (MRI), and, depending upon circumstances, neuropsychological testing, and a variety of hematologic and biochemical assays. However, the single most important laboratory study in understanding the nature of the seizure disorder in the affected patient remains, more than 70 after its invention, the electroencephalogram (EEG), The EEG records the electrical activity of the brain, and discloses the abnormal electrical patterns which are the hallmarks of the fundamental disturbance in epilepsy. Regardless of this critical role, standard EEG nevertheless has some severe limitations. One of these is that typically only 16-21 electrodes are applied to the scalp in conventional recordings, a practice that leads to relatively large distances between the recording electrodes. This, in turn, results in the long-held observation that localization of abnormal findings from standard EEG is usually very poor.
Recent and rapid technological advances are changing the current state of affairs, and leading to an expanded role for the EEG in the understanding of epilepsy and epileptic circuits. One of these advances is the capability to record from the scalp with a “dense array” of 256 EEG electrodes. With reduced interelectrode distances, spatial resolution is markedly improved, and approaches the mininum distance required to maximize the spatial information that can be extracted from scalp recordings. Furthermore, the 256 channel electrode net that is utilized in dense array recordings covers portions of the face and neck (in contrast to conventional EEG) and in this manner allows “sampling” of electrical activity from portions of the undersurface, or basal, brain regions. This capability is important, since seizures often originate in these regions. Dense array EEG recording is used in conjunction with sophisticated methods of EEG source analysis, mathematical tools that assist in determining where in the brain abnormal electrical patterns originate. Source analysis is used with realistic models of the head and brain in order to obtain accurate results. Dense array EEG recordings are possible for either short-term 1-2 hour recordings, or when required, for continuous longterm EEG video monitoring.
At the University of Washington Regional Epilepsy Center dense array EEG is being used to study patients with a variety of epilepsy syndromes. These studies are leading, in some cases, to novel insights into the cerebral cortical networks activated during epileptic discharges One study, for example, that examined patients with typical absence seizures, often regarded as prototypic generalized seizures, suggests that “generalized” seizures are not truly generalized. Rather, only restricted brain regions appear to be activated at the onset and during the propagation of the seizure. Cortical areas preferentially involved in absence include parts of the frontal lobe. Similarly, in a series of patients with juvenile myoclonic epilepsy (JME), a common generalized epilepsy syndrome in adults, highly restricted cortical areas are also found to be active during discharges, which usually include parts of the frontal and temporal lobes. In the future, knowledge of the pathologic neuronal circuitry in medically refractory generalized seizures may lead to novel approaches to treatment.
A major research focus at the Regional Epilepsy Center employs continuous longterm EEG-video monitoring using dense array EEG in order to capture seizures in medically intractable patients who are potential candidates for epilepsy surgery. To date, we have successfully monitored over 40 subjects for periods of 24-96 hours and have recorded clinical seizures in nearly all. Our goal is to compare the results of seizure onset and propagation, as predicted by dense array EEG, to standard methods of evaluation, including invasive EEG monitoring. The outcome in one case of a subject with refractory epilepsy forms the basis of optimism that dense array EEG recordings of partial seizures may, at least in some cases, accurately predict seizure onsets. In this patient, standard EEG recordings disclosed widespread, poorly localized interictal discharges and conventional longterm monitoring disclosed seizures that could not be localized. Prior to invasive EEG recordings, dense array EEG studies captured a clinical seizure and source analysis disclosed that the attack originated from left posterior inferior occipital cortex. This prediction was confirmed precisely on subsequent invasive recordings. The resection was carried out based on the results of the intracranial studies and the individual has been seizure-free nearly 30 months after the operation. To date, dense array EEG predictions of seizure onset have been confirmed, based on comparison with subsequent intracranial EEG recordings, in eight of ten patients. We anticipate that dense array EEG may one day reduce the need for invasive EEG recordings, and at the very least, help guide the placement of intracranial electrodes.
In the near future, work with dense array EEG will co-register an individual patient’s own MRI to the electrographic data. Research with this technology also includes investigations of EEG features unique to seizure onsets, and some investigators believe that recordings with up to 1000 EEG electrodes will be made in the future to extract the maximum possible information from scalp recordings. We may anticipate that the outcome of this research will be ever increasing accuracy in determining the nature and location of epileptic discharges in the brain using a safe and noninvasive technique.