Approximately 1% of the general population is afflicted with epilepsy. In many cases, seizures can be controlled with medication, but approximately 20% of patients with epilepsy fail to respond to anti-epileptic drugs or they have intolerable medication side effects. Effective surgical intervention requires accurate identification of the seizure onset zone and development of a surgical approach that minimizes damage to nearby healthy tissues. Many medical centers are now exploring the possible utility of noninvasive brain imaging methods for localizing the seizure focus. At the Hoglund Brain Imaging Center (HBIC, we are developing strategies for integrating data from multiple brain imaging methods for localization of epileptogenic tissues. Of particular note is our inclusion of Magnetoencephalographic (MEG) data. MEG involves measurement of the weak magnetic signals generated by the brain electrical activity. HBIC is one of only 12 U.S. centers with whole-head MEG technology. Figures 1-2 illustrate the principles of MEG.
Figure 1: Electrical currents flowing within the apical dendrites of pyramidal cells oriented parallel to the scalp surface generate a surrounding magnetic field that can be measured with super-cooled wires connected to SQUIDs.
Figure 2: Three seconds of example data are shown for 18 sensors over the left hemisphere. Each sharp deflection is an epileptic spike. The overall spatial pattern of magnetic flux for each spike can be specified by an iso-field contour map. Using mathematical procedures it is possible to infer the location of the neuronal currents that generate the recorded magnetic signals. This location can be marked on spatially aligned MR images. For the above figure, the point in green shows the site of origin for the highlighted spike. Purple points show source locations for other spikes in the dataset.
Available brain imaging methods at KUMC include: Magnetic Resonance Imaging (MRI), MR Spectroscopy (MRS), Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG) and Magnetoencephalo-graphy (MEG).
The patient is a 11 year old male with a history of medically refractory tonic-clonic and partial complex seizures beginning in the spring of 2002. Despite medication with Depakote and Dilantin, the patient continues to have 1-3 seizures per day. His most common seizure type is characterized by turning and walking in circles towards the left. He also grunts and/or hums during the seizures, each event lasting 1-2 minutes.
Prior MRI and SPECT were reported to be within normal limits. MEG and EEG recorded at HBIC revealed frequent epileptic discharges over the right temporal lobe. Spikes were more evident on the MEG than the simultaneous EEG (see figure 3), owing to the orientation of the relevant neuronal currents. Source modeling and integration of data with MRI showed the majority of spikes to arise from a focal region of the lateral temporal neocortex of the right hemisphere. Surgical resection of the implicated zone is not being planned.
Figure 3: Both MEG (black) and simultaneous EEG (red) show epileptic spikes, although these are more easily seen on the MEG. The MEG also shows heart-beat artifacts (channel EEG159 shows the EKG). Source modeling showed spikes to arise from the posterior aspects of the right temporal lobe.
The patient is a 16 year old female with a history of simple partial seizures that on occasion evolve to complex partial seizures. Most events begin with a peculiar sensation in the right hand and arm. She will then extend the right arm and hand. This may then be followed by some movement on the left, with clonic activity involving the left arm and hand. She is frequently left with a left hemiparesis that resolves. Despite multiple medications, she is poorly controlled.
Prior MRI at Mayo was interpreted as within normal limits but an MRI at MINCEP suggested a region of high left parietal midline dysplasia. PET and SPECT have been reported as negative. EEG has shown some diffuse slowing and irregular theta, generally without clear spikes (although one report suggests some left frontal spikes). Seizures are best characterized by parasagittal rhythmic theta, most prominent on the left. MRI at HBIC confirmed the MINCEP observation of a region of left parietal dysplasia. This same area was shown to have reduced NAA by MR spectroscopy. MEG showed theta bursting originating from this area, with additional involvement of the homologous area on the left (see figure 4). Surgical resection of the left parietal zone is planned.
Figure 4: MRI, MEG, and MRS each show a region of left parietal abnormality. The convergence of methods is allowing this patient to proceed to surgery.
The patient was an 8 year old female with simple partial seizures. Whole-head MEG and simultaneous EEG revealed frequent right sided spikes. Analyses of the MEG data revealed sources (white crosses) in the right parietal lobe, in a region normal by structural MRI.. SPECT imaging showed this same area to demonstrate hyperperfusion. Single voxel spectroscopy in this area and the contralateral region showed the right side to have reduced NAA, a sign of disruption of cellular metabolism. Surgical intervention in the right parietal area produced a seizure free outcome.
Figure 5: MEG, SPECT, and Spectroscopy data converge to show a right parietal abnormality. Surgical resection of the pathophysiological zone yields a seizure free outcome.
MEG is useful in the localization of regions of epileptic pathology. In patients with medically refractory epilepsy, integration of MEG data with data from EEG, MRI, SPECT, and MRS provides an effective, noninvasive strategy for localizing zones for surgical resection.
This work has been supported by grants from NIH, NSF, Picker International, and VSM Medtech.
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The University of Kansas Medical Center