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Dense Array EEG and Epilepsy



By Mark D. Holmes, M.D.

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The evaluation of epileptic seizures requires a detailed assessment of patient history, a clinical examination, and laboratory studies including standard electroencephalography (EEG), brain magnetic resonance imaging (MRI), and, depending upon circumstances, neuropsychological evaluation and various hematologic and biochemical assays. Despite major advances in neuroimaging, the single most important laboratory tool in the evalution of epilepsy remains the EEG. Nonetheless, standard scalp EEG has some severe limitations. In conventional recordings, 16–21 electrodes (10–20 internationally) are applied to the scalp. This results in interelectrode distances of several centimeters, which provide poor spatial resolution, so that localization of EEG findings from standard scalp recordings is limited, at best, to gross lobar or hemispheric regions.

Recent technological advances are likely to change this state of affairs and lead to an expanded role for the EEG in epilepsy. One advance is the ability to record from the scalp with a "dense array" of 256 EEG electrodes. With reduced interelectrode distances, spatial resolution is markedly improved, approaching the theoretical "spatial Nyquist" — the mininum interelectrode distance required to maximize spatial information from scalp recordings. Furthermore, the 256-channel electrode net that is utilized in dense array recordings covers portions of the face and neck, and, in contrast to conventional EEG, permits as much characterization as feasible of electrical activity arising from basal brain regions. Dense array EEG recording is used in conjunction with sophisticated methods of EEG source analysis and realistic models of head and brain anatomy. Solutions to source analysis are restricted to the cerebral cortex and the brain regions that generate the EEG, and the application of a standard MRI model allows analysis to take into account typical head and brain geometry and the electrical properties of cranial tissues. Dense array EEG recordings are possible for either short-term (one- to two-hour) recordings, or when required, long-term monitoring (up to 48–72 hours).

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Fig. 1
A patient wears an electrode net.
At the University of Washington Regional Epilepsy Center, dense array EEG is being used to study patients with both generalized and localization-related epilepsy syndromes. These studies are leading to novel insights into the neuronal network activated during epileptiform discharges. For example, one study that examined patients with typical absence — the prototypical generalized seizure — suggests that these seizures may not be truly "generalized." Rather, only restricted cortical areas are activated at the onset and during the propagation of spike-wave bursts. Cortical areas preferentially involved in absence include the frontopolar and mesial frontal cortex. Similarly, in a series of patients with juvenile myoclonic epilepsy (JME), a common generalized epilepsy syndrome, highly restricted cortical areas were also found to be active during discharges. In cases of JME, the orbitofrontal and temporal cortex are almost always involved, with less common activation of the mesial frontal, parietal, and occipital regions. In the future, knowledge of the pathologic neuronal circuitry in refractory generalized seizures may lead to novel treatments.

Dense array EEG may also disclose the complex dynamics of interictal epileptiform discharges in subjects with temporal lobe epilepsy. One important finding is that both temporal lobes frequently contribute sources during the time course of a single interictal spike, even when conventional EEG suggests exclusively unilateral localization. This observation gives credence to the notion that temporal lobe epilepsy is usually a bilateral process. Another finding is that extratemporal regions such as the orbitofrontal cortex may also be part of the cortical network activated during an apparent temporal discharge. One unanswered question remains: does the interictal spike recapitulate the epileptic circuit involved during the clinical seizure? Future research will address this question and others in order to place these new results in a useful clinical context.

The primary clinical role for dense array EEG at the Regional Epilepsy Center is to localize seizures in patients who are candidates for epilepsy surgery. We have successfully monitored subjects continuously for periods of 24–72 hours and have recorded seizures in nearly all of them. 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.
Topographic dense array EEG map
Fig. 2
The top half of the figure is a topographic dense array EEG map of the initial second of seizure onset, looking from the top of the head (nose at the top). The bottom half of the figure displays the source analysis of seizure onset, with origin at the left inferior occipital cortex (white voxels indicate maximal intensity).


The outcome in one case of a subject with refractory extratemporal epilepsy makes us optimistic that dense array EEG recordings of partial seizures may accurately predict ictal onsets. In this patient, standard EEG recordings disclosed widespread, poorly localized interictal spikes with left posterior quadrant preponderance, while conventional long-term 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 event originated in the 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 after the operation, the individual has been seizure-free for nearly 18 months. We anticipate that dense array EEG may one day reduce the need for invasive EEG recordings and at the very least will 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 (rather than a standard MRI model) to the electrographic data to obtain even more accurate spatial resolution to guide neurosurgical intervention.
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