2009 Clinical Year in Review

This article first appeared in our inaugural edition of our Clinical eNewsletter in February 2010.

It was a productive year for our clinical customers. We have noted 27 new publications in 2009 and the first few months of 2010.  Epilepsy was a major focus for our customer base, with 12 of the 27 publications having worked in this area. Several customer posters also focused on epilepsy at December’s Boston meeting of the American Epilepsy Society (AES).

In two of the AES posters (Lantz, Brodbeck, Seeck, Tucker, & Michel, 2009; Yamazaki, Fujimoto, & Yamamoto, 2009), dense array EEG (dEEG) was again shown to be superior to conventional EEG in its ability to accurately localize spike data. Lantz et al. found that the distance between the source focus location and the clinically determined focus location increased as the EEG channel count decreased (from good correspondence with 256-channel dEEG to poor correspondence with 32-channel EEG). In the report by Yamazaki et al., dEEG (256 and 128 channel) data yielded more focal localization results than that of the conventional (19 channel) data from the same patient. In a third AES poster (Spinelli et al., 2009), dEEG source imaging was shown to have a sensitivity and specificity for localization that was comparable to or better than those obtained with positron emission tomography (PET) and single photon emission computed tomography (SPECT).

The localization of the epileptogenic region using dEEG data has been shown to be superior to the localization results based on conventional EEG. How does this impact the guidance of intracranial electrode placement? For the answer, we look to 2010.

The early months of 2010 brought us two new exciting publications by Holmes et al. (2010a) and Brodbeck et al. (in press). Both studies examined patients with extra temporal lobe epilepsy (ETLE), and, in the case of Brodbeck et al., all patients exhibited normal MRI findings. Patients with ETLE are traditionally the most challenging as standard clinical workups often fail to localize the epileptogenic region, which leaves the neurologists with little information on the placement of intracranial electrodes, or even less desirable, leaves the patients as poor surgical candidates. In this difficult patient group, source imaging using dEEG data, from both ictal (Holmes et al., 2010b) and interictal (Brodbeck et al., in press) spikes, was in good agreement with the results of the intracranial electrode data. While dEEG by no means replaces intracranial electrodes, these results suggest that it may be useful in guiding the placement of the intracranial electrodes.

In cases with large brain lesions, it has long been argued that source localization derived from MEG data is more accurate than that derived from EEG data (Williamson and Kaufman, 1987). While EEG is more sensitive to deep sources and all source orientations compared to MEG, it is also more susceptible to conductivity variations. Large brain lesions are known to cause inhomogeneous conductivity within the skull. In Brodbeck, Lascano, Spinelli, Seeck, and Michel (2009), the authors used a head model constrained to an individual patient’s gray matter to investigate what effect this inhomogeneous conductivity would have on the source localization results. The conclusion was that high-resolution source imaging using dEEG identifies the epileptogenic focus with excellent accuracy even for patients with brain lesions.

Finally, we look to Michel and Seeck (2010) for a discussion of the imaging techniques used in preoperative assessments in pediatric epilepsy. Standard protocol calls for the use of invasive preoperative intracranial electrode recordings for an extended period of time. This procedure requires a large time commitment from hospital staff and cooperation from the patient and the patient’s family. Michel and Seeck ask if this procedure can, at least in part, be replaced by noninvasive techniques. They argue that, when used independently, neither dEEG nor fMRI gives both a complete mapping of the epileptogenic region as well as a functional mapping of all of the essential functions (such as language and motor functions). They suggest that a multimodal approach of simultaneous dEEG and fMRI recording may provide a more accurate picture.

With the fundamental building blocks for the utility of dEEG established, we now turn to case specific findings in 2009.

Use of antiepileptic drugs to treat patients with subclinical dEEG spikes has mixed results. While antiepileptic drugs can reverse symptoms in some populations, others continue to demonstrate further deterioration in cognitive function in spite of, or perhaps as a result of, side effects from pharmacological treatment. Children with both attentional/learning difficulties and subclinical spikes treated in an open-label trial with Levetiracetam showed significantly greater than expected post treatment assessment scores, as well as spike suppression, in their dEEG data (Mintz et al., 2009).

Understanding the Origin of the Spike-wave Seizure

Much can be learned from animal models, but they often fall short of simulating the full complexity of human experience. Decades of work exist on animal models aimed at understanding spike-wave (SW) seizures and their connection with precursory cortical slow oscillations (CSO). See Amzica (2009) for an excellent overview of these past animal studies. How does the human model compare? Tucker, Waters, and Holmes (2009) examines the case of one patient with daily multiple SW seizures finding that the SW seizure onset localized to both the left frontal pole (also the primary source of the CSOs) and to the left temporal lobe during the propagation of the seizure. They concluded that the correlation of SW seizures with CSOs in animal studies might be observed in humans as well, which may provide clues to the pathology of arousal regulation in some cases of nocturnal epilepsy.

Our understanding of neurophysiology circuits is limited by our ability to accurately observe and quantify the phenomenon. Until recently, juvenile myoclonic epilepsy (JME) has been characterized in the literature as having generalized epileptiform discharges. Holmes, Quiring, and Tucker (2010b) shows that by using dEEG rather than conventional EEG, the epileptiform patterns in JME are actually highly localized to specific cortical regions. This is true for both the onset and during the subsequent propagation of discharges. In addition, new evidence exists (Tucker & Holmes, 2009) that there are separable mechanisms of orientation in the limbic networks of consolidated memory and consciousness in the frontothalamic circuits. Now that, using dEEG, it is possible to localize the generalized spike-wave (GSW) seizures, we are beginning to understand this neural circuitry.

In summary, 2009 was truly a remarkable year. Our customers have made important contributions to the understanding and treatment of epilepsy. Interested in learning about more work that used EGI’s Geodesic EEG System? Click here to contact EGI. 

Brodbeck, V., Lascano, A.M., Spinelli, L., Seeck, M., Michel, C.M. (2009). Accuracy of EEG source imaging of epileptic spikes in patients with large brain lesions. Clinical Neurophysiology, 120, 679-685.

Brodbeck, V., Spinelli, L., Lascano, A.M., Pollo, C., Schaller, K., Vargas, M.I., Wissmeyer, M., Michel, C.M., Seeck, M. (in press). Electrical source imaging for presurgical focus localization in epilepsy patients with normal MRI. Epilepsia.

Holmes, M.D., Tucker, D.M., Quiring, J.M., Hakimian, S., Miller, J.W., Ojemann, J.G. (2010a). Comparing Noninvasive dense array and intracranial electroencephalography for the localization of seizures. Neurosurgery, 66(2), 1-10.

Holmes, M.D., Quiring, J., Tucker, D.M. (2010b). Evidence that juvenile myoclonic epilepsy is a disorder of frontotemporal corticothalamic networks. NeuroImage, 49, 80-93.

Lantz, G., Brodbeck, V., Seeck, M., Tucker, D.M., Michel, C. (2009, December). Electric source imaging – Increasing the number of electrodes to 256 improves source localization precision of Interictal epileptiform activity. Poster session presented at the 63^rd Annual Conference of the American Epilepsy Society, Boston, MA

Michel, C.M., Koenig, T., Brandeis, D., Gianitti, L.R.R., Wackermann, J. (Eds.). (2009). Electrical Neuroimaging. Cambridge: Cambridge University Press.

Michel, C.M., Seeck, M. (2010). New imaging techniques in pediatric epilepsy surgery. In Cataltepe O. & Jallo G. (Eds.), Pediatric Epilepsy Surgery: Preoperative Assessment and Surgical Treatment (pp. 348-356). New York: Thieme.

Mintz, M., LeGoff, D., Scornaienchi, J., Brown, M., Levin-Allen, S., Mintz, P., & Smith, C. (2009). The Underrecognized Epilepsy Spectrum: The Effects of Levetiracetam on Neuropsychological Functioning in Relation to Subclinical Spike Production. Journal of Child Neurology, 24(7), 807-815.

Spinelli, L., Brodbeck, V., Lantz, G., Pollo, C., Schaller, K., Vargas, M., … Seeck, M. (2009, December). Sensitivity and specificity of EEG Source Imaging (ESI) for focus localization in the presurgical evaluation. Poster session presented at the 63^rd Annual Conference of the American Epilepsy Society, Boston, MA

Tucker, D., & Holmes, M. (2009, December). Seizure disorders may imply separable mechanisms of orientation and conscious attention. Poster session presented at the 63^rd Annual Conference of the American Epilepsy Society, Boston, MA

Tucker, D.M., Waters, A., & Holmes, M.D. (2009). Transition from cortical slow oscillations of sleep to spike-wave seizures. Clinical Neurophysiology, 120(12), 2055-2062.

Williamson, S.J., & Kaufman, L. (1987). Analysis of Neuromagnetic Signals. In A.S. Gevins, & A. Rémond (Eds.). Handbook of electroencephalography and clinical neurophysiology: Methods of Analysis of Brain Electrical and Magnetic Signals (pp. 405–48). Amsterdam: Elsevier

Yamazaki M, Fujimoto A, Yamamoto T. (2009, December). The new trend of long-term video EEG monitoring using dense-array EEG for patients with medically refractory epilepsy. Poster session presented at the 63^rd Annual Conference of the American Epilepsy Society, Boston, MA