Cortical dysplasia

The purpose of this study is to investigate if multimodality neuroimaging evaluation increases the detection of subtle focal cortical dysplasia as part of an epilepsy surgery evaluation. Three patients with normal magnetic resonance imaging and histopathological findings of focal cortical dysplasia were reviewed. Their magnetoencephalography recordings were performed on whole-head magnetoencephalography system. Magnetic resonance images were re-evaluated with special inspection in limited regions guided by magnetoencephalography spike localization. Two patients had ictal and interictal single photon emission computed tomography study after administration of Tc99m ECD. In two patients we found tiny focal abnormalities including slightly increased cortical thickness and blurred gray-white matter junction at the locations of interictal events after re-evaluation of the MR images indicating focal cortical dysplasia. The third patient showed focal atrophic change. All patients are seizure free after surgery. Both ictal and interictal single photon emission computed tomography showed hyperperfusion in the dysplastic cortex regions. Multimodality neuroimaging study can improve the detection of focal cortical dysplasia. Normal magnetic resonance images should be re-evaluated for subtle signs of focal cortical dysplasia especially when magnetoencephalography recording demonstrate focal epileptic discharges. [Neurol Res 2003; 25: 53-57]

Keywords: Magnetoencephalography; magnetic resonance imaging; focal cortical dysplasia; single photon emission computed tomography; epilepsy

INTRODUCTION

Focal cortical dysplasia (FCD), a type of neuronal migration disorder, was originally described by Taylor et al.1. Its histopathological features include disruption of cortical lamination associated with an excess of large aberrant neurons and an increase of cortical thickness. FCD is the most common developmental disorder in candidates for epilepsy surgery2. The detection of FCD mainly depends on magnetic resonance (MR) imaging. The clinical semiology and scalp electroencephalography (EEG) often fail to provide precise localization of the epileptogenic focus. Searching for subtle cortical abnormalities on MR images in a systemic way is challenging3. In this situation, long-term invasive EEG monitoring is frequently the only choice for pre-surgical evaluation4.

Magnetoencephalography (MEG) is a novel noninvasive technique based on the capacity of super-conducting interference device (SQUID) sensors to detect magnetic flux produced by the intracranial currents. After the electromagnetic sources are overlaid on MR images, the localization accuracy can be within a few millimeters in patient or phantom5,6. Single photon emission computed tomography (SPECT) can localize the epileptogenic foci by showing the hemodynamic changes ictally and interictally in epilepsy patients. In order to improve the detection of FCD and possible avoidance of pre-surgical invasive evaluation, we re-evaluated the MR images in three epilepsy patients with normal MRI, who had SPECT, MEG recording and FCD histopathological findings.

MATERIALS AND METHODS

During 1997 to 2001, 20 epilepsy patients with cortical developmental disorders were operated at the Texas Comprehensive Epilepsy Program and underwent an MEG study. Within this group, three patients (C.G., E.C., N.P.) with intractable partial complex seizure and normal MRI report were evaluated. Two patients were female (aged 3, 6 years) one was a 15-year-old boy. MR examinations were performed on a 1.5 T magnet system (GE Signa, Milwaukee, WI, USA). A standard epilepsy MRI protocol was acquired in all patients, including T1-and T2-weighted spin echo (SE), three dimensional fast spoiled gradient recalled (3D SPGR) and fluid attenuated inverse recovery (FLAIR) sequences. MR images were reevaluated after getting localization information from MEG data.

MEG recordings of spontaneous brain activity were obtained with a 148 channel whole-head magnetometer (Magnes WH2500, 4-D Neuroimaging, San Diego, CA, USA) in a magnetically shielded room. Simultaneous EEG was recorded with gold disc electrodes using a bipolar montage (Neurofax, Nihon-Kohden, Tokyo, Japan) from 21 scalp locations, based on the International 10-20 system. Two children (C.G. and E.C.) were sedated with chloral hydrate (35 to 75 mg kg^sup -1^) for the MEG study.

The MEG was recorded for 20-30 min with a sampling rate of 508 Hz and an online bandpass set between 0.1 and 100 Hz. The recording period lasted 20-30 min. The data were first filtered between 3-70 Hz, and then inspected to identify electromagnetic events that temporally coincided with epileptiform electrical discharges. The intracranial locations of the currents that produced those electromagnetic events were modeled as equivalent current dipoles (ECD). The MEG data were coregistered on the 3D-SPGR MR images (24 cm field of view, 256x256 matrix and 1.4 mm slice thickness) with the help of three common fiducial points ( the nasion and the left and right external meati).

Ictal and interictal SPECT studies were performed in two patients (C.E., P.N.) using Tc99m ECD on a whole body SPECT nuclear imaging system (Triad 88, Trionix Research Lab, Inc, Twinsburg, OH, USA). All the three patients conventionally underwent chronic intracranial video-EEG monitoring prior to surgery.

RESULTS

All patients showed frequent interictal epileptogenic discharge activities during the MEG study. One patient showed frequent, large amplitude electromagnetic bursting epileptiform activities and frequent isolated interictal spikes, the other two patients mainly showed frequent multiple isolated interictal spikes (Figure 7). When overlaid on MRI, the intracranial sources of their events clustered in the right anterior medial frontal lobe (C.G.), the left frontal central area (E.C.), or the right lateral frontal lobe (N. P.). A careful re-evaluation of the patients' MRIs showed slightly increased focal cortical thickness and blurred white-gray matter in two patients (E.C., C.G.) indicating the presence of FCD. Patient E.C. in particular showed mildly increased signal intensities in the dysplastic cortex and underlying white matter extending to the lateral ventricle. There were no direct signs indicating the presence of FCD, but focal subtle cortical atrophy was found in the third patient (N.P.). The concordance of MEG dipole localization and MRI structural abnormalities was excellent, all activity source clusters overlapped with the structural abnormalities (Figures 2-4). There were no size and signal intensity changes in the hippocampus on MRIs. The post-ictal SPECT showed increased regional cerebral blood flow in the structural abnormal regions, but in other regions as well (Figure 2), while interictal SPECT showed increased blood flow restricted to the abnormal regions (Figure 2). Surgery was performed after long-term intracranial EEG monitoring. The intra-operative ECoG findings confirmed the localization in all cases. Patient C.G. underwent a frontal lobectomy, patient N.P. a lesionectomy, and patient E.C. a partial lesionectomy and multiple subpial transection.

Histopathological findings showed dysmorphic neurons in the corresponding areas with balloon cells (FCD type IIb)7. Patients were seizure free after six months to 1 year follow-up.

DISCUSSION

Magnetic resonance (MR) imaging is considered as the method of choice for the pre-surgical evaluation of epileptic patients with suspected FCD. The MR findings of FCD include variable degrees of cortical thickness, blurred gray and white matter junctions, and hyperintense signal within the lesion and underlying white matter. The development of MR techniques, such as thinner slice thickness, higher-resolution, morphological processing methods (multi-planar reformatting-MPR or curvilinear multi-planar reformatting-CMPR), has increased the detection of subtle FCD3,8. However, in many cases, the FCD abnormalities are too subtle to be recognized or detected by standard radiological analysis9. MRI is usually obtained at an earlier stage during the pre-surgical evaluation of epileptic patients. If the MRI is normal, long-term invasive EEG monitoring is performed by using extensive intracranial electrodes. Given the difficulties in identifying the epileptogenic zone and associated less favorable surgical outcomes, the utility of surgical intervention has been questioned10.

In view of the difficulty associated with surgical management of FCD, integrating information from multiple noninvasive techniques, such as SPECT, scalp V-EEG, and MEG may be particularly useful. Due to the intrinsic epileptogenic feature11-14, MEG can be used successfully in FCD to reveal the location of both ictal and interictal epileptogenic activity in close agreement with electrocorticography14. In general, concordance between scalp-EEG and MRI is not very high16. In the present study the desirable concordance with MRI was readily achieved by interictal MEG. In fact MEG helped identify the evidence of cortical pathology on MRI scans initially evaluated as normal. Therefore, MEG, (and SPECT as discussed below) could be readily used to guide the placement of intracranial electrodes in cases of suspected FCD17, and may also help detect more signs on MRI. It may be possible to decrease the number of chronic intracranial EEG monitoring when localization information from neuroimaging (such as, MEG, SPECT and MRI) are highly concordant15.

Standard epilepsy protocol usually includes spin echo (SE), spoiled gradient recalled (SPGR), flow attenuated inverse recovery (FLAIR) and diffusion weighted sequences. SPGR may be the favored sequence for the detection of subtle FCD due to its thinner slice thickness, good gray-white matter contrast and potential ability for further image processing. FLAIR can show mild signal change, this may benefit some balloon cell type FCD. However some subtle FCDs lack of signal intensity changes18,19. Although some authors stressed the importance of FLAIR15,20, we believe SPGR combined with FLAIR can show FCD better. In our series, one patient's MRI appearance is similar to a previous report18,19: FCD with balloon cells showed high signal intensity on T2-weighted and FLAIR images leading to the lateral ventricle. The other two patients did not have signal changes although their pathological findings indicate FCD with balloon cells.

Previous reports have shown that SPECT, especially the ictal studies are very useful for the epileptogenic localization21,22. The ictal SPECT usually shows hyperperfusion wherever interictal SPECT shows hypoperfusion. But in our series, two patients showed hyperperfusion in both ictal and interictal scans. While the region of increased blood flow in the interictal SPECT were eventually co-extensive with the region showing structural abnormalities, the pattern of hyperperfusion in the ictal SPECT was significantly more diffuse. The presence of very frequent interictal epileptiform activity can be responsible for the hyperperfusion in these areas23,24. The interictal hyperperfusion region showed better concordant to MRI, MEG and invasive EEG recordings in our patients. For this patients' group, interictal SPECT abnormalities may be more specific for localization given the diffuse nature of blood flow changes on ictal SPECT scan.

CONCLUSION

Multimodality neuroimaging evaluation can increase the detection of subtle cortical abnormalities. Interictal SPECT may provide more precise localization of subtle FCD. It might be possible to decrease the number using chronic invasive EEG monitoring if the localization findings from MEG, MRI, SPECT and other resources are highly concordant. We suggest that re-evaluation of normal MRIs may be necessary if localization information is available from electromagnetic recordings, SPECT or other imaging methods.

ACKNOWLEDGEMENTS

We wish to thank Mr Eric Y. Caballero, 4-D Neuroimaging Inc., and Ms Juliap K Kmulwa, Memorial Hermann Hospital Nuclear Medicine, for their technical assistance. This study was supported in part by NIH Grant NS37941-01 to Dr A.C. Papanicolaou.

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Wenbo Zhang*, Panagiotis G. Simos*, Hideaki Ishibashi*, James W. Whelessr[dagger][double dagger], Eduarde M. Castillo*, Howard L. Kim[double dagger], James E. Baumgartner[dagger], Shirin Sarkari* and Andrew C. Papanicolaou*

* Department of Neurosurgery, [dagger] Department of Pediatrics, [double dagger] Department of Neurology Vivian L. Smith Center for Neurologic Research, Texas Comprehensive Epilepsy Program, The University of Texas - Health Science Center at Houston, Houston, TX, USA

Correspondence and reprint requests to: Wenbo Zhang, MD, PhD, Vivian L Smith Center for Neurologic Research, Division of Clinical Neuroscience, Department of Neurosurgery, The University of Texas Health Science Center at Houston, 1333 Moursund Street Ste H114, Houston, TX 77030, USA. [wenbo.zhang@uth.tmc.edu]. Accepted for publication July 2002.

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