Localizing Seizure Activity - An Interview with Hal Blumenfeld, MD, PhD
Recently Dr. Blumenfeld was featured in The Yale Bulletin: Findings set stage for prevention of epilepsy. Here is a link to that article. Also, we are presenting again for you, an interview feature with epilepsy.com / The Editors.
Hal Blumenfeld, MD, PhD, is Director of Medical Studies in Clinical Neuroscience at the Yale School of Medicine where he is Associate Professor of Neurology, Neurobiology, and Neurosurgery. His undergraduate training was at Harvard, where he majored in bioelectrical engineering, and he completed his MD and PhD at Columbia University. Dr. Blumenfeld's research is focused on understanding network mechanisms that generate epileptic seizures, and on resulting behavioral impairments, particularly loss of consciousness – with an ultimate goal of finding new therapeutic options in the treatment of epileptic disorders.
He has developed a method of localizing seizure onset using a tracer dye and single photon emission computed tomography (SPECT). The tracer is injected during a seizure (ictal SPECT). Then to arrive at greater accuracy, he performs Statistical Parametric Mapping (SPM), which he uses as an objective tool for analyzing ictal vs. interictal SPECT scans. Interictal SPECT analyzed by SPM (ISAS) was introduced and validated in two recent studies (Chang, DJ et al. Epilepsia, 2002, and McNally, KA et al., Epilepsia, 2005 – see reference articles).
In a recent interview, epilepsy.com asked Dr. Blumenfeld about his work.
Q. Why did you decide to employ this technique?
A. We found in trying to analyze ictal SPECT studies that the interpretation of the imaging results was often subjective. As it happened, during this same time, new tools were being developed for statistical analysis for brain imaging data called SPM (http://www.fil.ion.ucl.ac.uk/spm/). We decided to use this approach and develop a new way to use SPECT imaging to identify the region of seizure onset.
Q. How do you use this technique clinically?
A. When our patients, ranging from children to adults, are already in the hospital for standard clinical EEG monitoring, we obtain a SPECT image so that we can do an analysis to objectively identify areas of significantly increased blood flow that correspond to areas of seizure onset. We do this using a process that is based on injecting a tracer dye during a seizure that highlights part of the brain and helps us identify the region of seizure onset. The image obtained during a seizure is compared to a baseline image obtained when the patient is not having a seizure. This helps the neurologist make better decisions and helps us to appropriately plan for surgery.
Q. Tell us about your research using this technique.
A. By using SPM methods to analyze SPECT images, we are able to better understand the relationship between brain areas involved in seizures and imaging changes found with SPECT. Through our research we have recently validated the method on a group of patients where the region of seizure onset was known. Our goal has been to show that this method is clinically useful.
For example, we showed that the time of injection is critical to correctly identify the region of onset; whereas injection after the seizure is over is much less helpful. With this approach we were able to identify a single unambiguous region of onset accurately over 70 to 80 percent of the time. (McNally, DJ et al.)
We are also using similar SPECT analysis methods to help us identify regions of the brain that are crucial for loss of consciousness during seizures. In addition, we are carrying out another study using fMRI to identify brain regions that cause loss of consciousness in childhood absence epilepsy (http://www.clinicaltrials.gov/ct/show/NCT00393666?order=5). Loss of consciousness in epilepsy has a significant impact on patient quality of life, and more studies are needed in this area.
Q. How does this differ from methods being utilized at other epilepsy surgery
A. This method has several advantages. Ictal and interictal images are subtracted so that the difference can be obtained. This is useful because sometimes SPECT changes during seizures can not be identified accurately (e.g. by visual interpretation) until compared quantitatively with baseline interictal images.We see another advantage when the difference from ISAS results is compared to a normal database. When imaging changes are seen in a patient’s difference image (ictal vs. interictal) it is not always possible to know if the changes are significant, or just represent “noise” due to random fluctuations. To address this, we compare each patient’s results to a database of healthy normal SPECT pairs to determine if the changes in the patient (ictal vs. ictal) are beyond what is expected from doing two SPECT scans even when a seizure is not present. If it is determined that changes are statistically significant, then objective criteria are provided for interpreting images. In this way a seizure focus can reliably be identified.
Q. Why did you make this available to health care professionals?
A. We found the method to be clinically useful at our center and hope that other epilepsy centers will find it useful as well in taking care of their patients.
We did not want to spend many years going through the patent process, etc. in the hope of making a profit. We wanted to make it available right away. This analysis can be done using a software package called SPM intended for clinicians and researchers. Our method is available -- at no cost -- through: http://spect.yale.edu/
I want to point out that this is a relatively quick and easy method, once it has been set up by appropriately trained personnel. Our hope is that other epilepsy centers can make use of these methods so that they can improve patient care as quickly as possible.
- Blumenfeld H, Rivera M, McNally KA, Davis K, Spencer DD, Spencer SS.
Ictal neocortical slowing in temporal lobe epilepsy. Neurology 63: 1015-1021.
- Chang DJ, Zubal IG, Gottschalk C, Necochea A, Stokking R, Studholme C, Corsi M, Slawski J, Spencer SS, Blumenfeld H. Comparison of statistical parametric mapping and SPECT difference imaging in patients with temporal lobe epilepsy. Epilepsia. 2002 43(1): 68-74.
- McNally KA, Paige AL, Varghese G, Zhang H, Novotny EJ, Spencer SS, Zubal IG, Blumenfeld H. (2005). Localizing Value of Ictal-Interictal SPECT Analyzed by SPM (ISAS). Epilepsia. 46(9): 1450 –1464.
- Nersesyan H, Hyder F, Rothman D, Blumenfeld H. (2004). Dynamic fMRI and EEG recordings during spike-wave seizures and generalized tonic-clonic seizures in WAG/Rij rats. J Cereb Blood Flow Metab. 24(6): 589-599.
Reviewed and revised January 2007 by Steven C. Schachter, MD, epilepsy.com Editorial Board.
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