Contribution of SISCOM Imaging in the Presurgical Evaluation of Temporal Lobe Epilepsy Related to Dysembryoplastic Neuroepithelial Tumors


Address correspondence and reprint requests to Dr. I. J. Namer at Institut de Physique Biologique, Faculté de Médecine, 4, rue Kirschleger, 67085 Strasbourg Cedex, France. E-mail:


Summary:  Purpose: Dysembryoplastic neuroepithelial tumors (DNTs) are a group of glioneuronal supratentorial and intracortical lesions often associated with the early onset of intractable and crippling partial seizures. They are characterized by their location, multinodular architecture, and heterogeneous cell composition, with a specific glioneuronal element in the specific form. Foci of cortical dysplasia may be associated with the tumoral lesion, and identifying the presence and the extent of cortical dysplasia is not always easy on magnetic resonance images (MRIs). The purpose of this article is to evaluate, retrospectively, the usefulness of ictal single-photon emission computed tomography (SPECT) imaging to assess the presence and the extent of cortical dysplasia associated with DNTs in nine patients with intractable temporal lobe epilepsy related to histopathologically confirmed DNTs.

Methods: The results of the subtraction of ictal and interictal SPECT coregistered to MRI (SISCOM) were compared with the results of the examinations of pathological material after surgery.

Results: SISCOM showed a strongly hyperperfused area corresponding anatomically to electroclinical abnormalities and to the location of DNTs on MRI. A circumscribed hyperperfusion was present in DNTs without cortical dysplasia, limited to the location of the tumor on MRI. In cases of associated cortical dysplasia, a widespread hyperperfusion including areas corresponding to normal perilesional regions on MRI was found.

Conclusions: SISCOM, used among presurgical investigations, contributes to detecting cortical dysplasia associated with DNTs. Concordance between the symptomatogenic zone (defined from the medical history and electroclinical data), MRI scans, SISCOM pattern, and complete resection of the epileptic zone was predictive of a good postsurgical outcome.

Dysembryoplastic neuroepithelial tumors (DNTs) were described in 1988 by Daumas-Duport et al. (1) as a new type of brain tumor with the early onset of intractable and crippling partial seizures, without neurologic deficit. DNTs have been recently included in the revised World Health Organization classification in the category of “neuronal and mixed neuroglial tumors”(2). The morphologic and histopathologic features are the cortical location, the specific glioneuronal element, a multinodular architecture, and foci of cortical dysplasia (1,3). A histopathologic subclassification of DNTs into complex and simple forms was introduced according to the presence or absence of a glial nodule associated with the specific glioneuronal element (3). More recently, lesions with typical clinical and imaging DNT features but lacking the specific glioneuronal element have been defined as nonspecific DNTs (4). As with typical DNTs, nonspecific lesions also may be associated with cortical dysplasia. DNTs are located preferentially in the frontal or temporal lobes (1,5,6), but various locations have been described in the literature (7–10). Because they are benign, DNT diagnosis is essential to avoid unnecessary, deleterious, aggressive radio- or chemotherapy.

Epileptic surgery for DNTs is indicated in case of drug-resistant and crippling seizures, and a good postoperative outcome requires the complete resection of the DNT, including the dysplastic cortex. When present, the surrounding dysplastic cortex is usually epileptogenic per se (8,10–13) and associated with widespread cortical and subcortical network disturbance. Therefore its preoperative diagnosis and complete resection is mandatory to obtain a seizure-free outcome. Despite the development of high-resolution techniques, the identification of cortical dysplasia and the evaluation of its extent remain particularly difficult with conventional magnetic resonance imaging (MRI). Furthermore, subtle and diffuse cytoarchitectural cortical abnormalities (e.g., the microdysgenesis lesions) are not always visible macroscopically (8).

In this multidisciplinary retrospective study of nine histopathologically confirmed DNTs related to drug-resistant temporal lobe epilepsy, we investigated the usefulness of the subtraction of ictal and interictal single-photon emission computed tomography (SPECT) coregistered to MRI (SISCOM) to assess the presence and the extent of cortical dysplasia surrounding the DNTs.


Patient selection

Nine patients (Table 1) with drug-resistant partial seizures of the temporal lobe, according to the revised classification of the International League Against Epilepsy (14), related to histopathologically confirmed DNTs form the basis of this study. Details of pregnancy and delivery, history of febrile convulsions, patient age at the onset of seizures and surgery, type and frequency of seizures, and neurologic examinations were reviewed. The clinical features of the seizures and their chronology were carefully studied. Neuropsychological examinations were carried out in all cases, and a preoperative amobarbital test (Wada) or functional MRI was performed when necessary.

Table 1.  Clinical features, tracer injection delay, histopathological findings, surgical strategy, and follow-up
 Age (yr) and sexAge at seizure onset (yr)Length of seizures in ictal SPECTInjection delay of 99mTc-ECDHistopathologySurgery treatmentSurgical follow-upOutcomea
  • DNT, dyembryoplastic neuroepithelial tumor; SPECT, single-photon emission computed tomography; ECD, electron capture detector.

  • a

     Seizure outcome classified by Engel's criteria (15).

125 F221′23″13″Simple DNTStandard lobectomy21 moIA
221 F18 36″3″Nonspecific DNT with dysplasiaLesionectomy + adjacent cortex16 moIA
323 M161′10″15″Complex DNTStandard lobectomy16 moIA
418 F121′27″5″Nonspecific DNT without dysplasiaLesionectomy + adjacent cortex36 moIA
520 F14′42″30″Nonspecific DNT with dysplasiaLesionectomy + adjacent cortex34 moIA
628 M12 23″6″Nonspecific DNT with dysplasiaStandard lobectomy15 moIA
716 M41′16″16″Complex DNT1. partial lesionectomy;
2. standard lobectomy
6 yr,
  27 mo
827 M20 33″2″Complex DNTStandard lobectomy34 moIA
946 F131′21″3″Nonspecific DNT without dysplasiaStandard lobectomy10 moIA

All patients underwent several awake and sleep video-EEG monitoring, neuroimaging (ictal and interictal SPECT, MR studies including T2-weighted, diffusion-weighted, inversion-recovery T1-weighted, and gadolinium-enhanced imaging), and psychometric evaluation.

All patients underwent surgery, and an attempt was made to resect the epileptogenic area defined preoperatively. This area was resected en bloc, and the anterior, lateral, and superior aspects of the specimen were indicated to the pathologist to correlate the imaging data to the histopathologic examination. All resected specimens were examined both macroscopically and histologically. Particular care was taken to evaluate the presence, the location, and the extent of cortical dysplasia surrounding the DNTs. Seizure control after surgery was evaluated during the follow-up period and scored according to Engel's classification (15).

SPECT imaging and SISCOM

SPECT imaging studies were done with a low-energy, high-resolution, double-head camera (Elscint Helix, Hai-fa, Israel) using 740–925 MBq of 99mTc-electron capture detection (ECD; Neurolite; Du Pont, Wilmington, DE, U.S.A.). The camera was operated in the “stop and shoot” mode, with acquisitions at 3-degree intervals and a total acquisition time of 30 min (120 projections, 64 × 64 matrix). Slices were reconstructed by filtered backprojection by using a Metz filter [full width at half maximum (FWMH) of 8 mm] and displayed in a 128 × 128 matrix. The interictal studies were performed after a 24-h seizure-free period. Video-EEG recording was used before and during isotope injection to assess interictal activity at the exact time of injection. For ictal studies, patients underwent continuous video-EEG monitoring, and the isotope was injected immediately after the clinical onset of a seizure. Slices were acquired 30 min after the injection of ECD.

The MR studies used for SISCOM were obtained with a 3D inversion–recovery gradient-echo sequence, using a 25.6-cm field of view and a 128 × 128 × 128 matrix.

SISCOM images were obtained on a Hewlett-Packard C320 workstation using the 3D medical image analysis software MEDIMAX, developed at the Institute of Biophysic of Strasbourg ( The procedure consisted of three steps:

  • • SPECT–MRI registration: The ictal and interictal SPECT images were successively registered on the MRI by using a fully automated data-driven registration algorithm. This algorithm relies on a robust voxel similarity-based method that enables accurate rigid registration of dissimilar multimodal 3D images (16,17). To evaluate the technique's performance to register partially overlapping images, we participated in the evaluation project: “Evaluation of retrospective image registration,” National Institutes of Health, no. 1 RO1 NS33926-01; principal investigator, J.M. Fitzpatrick, Vanderbilt University, Nashville, TN, U.S.A. ( C. Nikou et al.).
  • • Ictal–interictal difference: To obtain the difference SPECT, first, interictal SPECT images were subtracted from ictal SPECT images; and second, each voxel of this subtracted image was divided by the mean voxel value of the interictal SPECT. The result was represented as a percentage of cerebral perfusion variation relative to the interictal SPECT.
  • • Fusion of MRI difference SPECT images (SISCOM). In this study only positive variations have been retained to create the SISCOM images.

SISCOM imaging studies were performed in all cases. Patient 7 underwent two surgical procedures, and the SISCOM imaging study was performed after the first surgical treatment.

Data analysis

Blind reinterpretation of MRI and SISCOM was performed by two experienced specialists (J.L.D. and I.J.N., respectively), without prior knowledge about the results of electroclinical and histopathologic data. The diagnostic criteria for both methods were based on qualitative visual analysis. With respect to the SISCOM studies, perfusion variation by ≥10% was regarded as significant. In all cases, the preoperative SISCOM data also were superimposed on the postoperative MRI for the evaluation of the limits of resected tissue. The abnormality seen with each method was compared with electroclinical data, postoperative results, and the location of histopathologic abnormality from the consensus of all authors.


Clinical data

The mean age at seizure onset was 12.9 ± 6.9 years (range, 18 months to 22 years). The duration of epilepsy before surgery was 11.1 ± 9.9 years (range, 2–33 years). In all cases, the patients had two or more drug-resistant, crippling seizures per day. Five patients had secondary generalization of partial seizures. One patient (case 5) had a history of premature delivery (35 weeks), followed by speech difficulties. One patient (case 1) had a sporadic neurofibromatosis type 1.

Ictal semiology was characterized by an “aura” with experiential contents, such as “déjà vu” associated with an epigastric aura in three patients, and acoustic phenomena in two. In those and in the remaining patients, the initial objective seizure sign was staring, associated with or followed by motor restlessness, oroalimentary automatisms such grimacing, chewing, lip smacking, swallowing, and vocalization, or stereotyped movements of arms or hands. Hypersalivation, when present, was a late sign. Contralateral ictal dystonic posturing of arms was found in four patients. Head orientation or deviation was never a lateralizing sign in our patients. Clear early ictal and postictal aphasia occurred when the critical activity onset involved the dominant hemisphere, but postictal aphasia also was present in patients in whom critical activity diffused from the nondominant to the dominant hemisphere.

Neurologic examinations were normal in all cases.

EEG data

Awake and sleep EEG monitoring showed interictal sharp waves, spikes, and spikes-and-slow-waves restricted to the temporal lobe in five patients (cases 1, 5, 7, 8, and 9) and widespread to the frontotemporal lobe in the remaining patients (cases 2, 3, 4, and 6). One patient had interictal polymorphic and intermittent slow activity, without spikes, localized in the temporal lobe (case 9). In patient 3, interictal abnormalities involved both temporal lobes and were asynchronous and independent.

Partial seizures were recorded in all cases during video-EEG investigations (including stereo-EEG in case 8), with an onset of critical activity in the temporal area demonstrating a good correlation between the location of the EEG abnormalities and the location of the lesion. Ictal EEG was characterized by focal low-voltage fast activity followed by rhythmic discharges of shape waves, spikes, and spikes-and-waves in the temporal lobe. In no cases were independent bilateral partial seizures recorded.

MRI data

On the basis of MRI characteristics and clinical data, the diagnosis of DNT was highly suspected in eight patients. In case 7, the lesion had been previously misdiagnosed as glial tumor on preoperative MR scans. In all cases, a cortical focal mass, exceeding the normal thickness of the cortex, was identified. A cystic component was present in eight cases, and moderate contrast enhancement was observed in one patient (case 6). In no cases were foci of cortical dysplasia surrounding the DNTs clearly identified.

In four patients (cases 2 through 5), the lesion was located in the lateral structures of the temporal lobe. In those cases, a deformity of the adjacent skull was observed. In case 9, the lesion involved only the temporomesial areas (amygdaloid nucleus). The remaining patients had an involvement of both mesial and polar structures of the temporal lobe.

All patients underwent two or more preoperative MRIs, and there were no significant radiologic changes in tumor shape and size.


In all patients, interictal and ictal SPECT findings were concordant with the electroclinical data regarding the localization and lateralization of the epileptic focus. In all cases, ictal SPECTs were performed for comparable critical patterns (from an electroclinical point of view: onset, length, and propagation characteristics), and with similar tracer delays for SPECT acquisition. SISCOM studies showed a strongly hyperperfused area corresponding anatomically to the electroclinical data and DNT location on the MRI. The hyperperfused area included the cystic component when present.

In six patients with DNTs associated with cortical dysplasia (three specific, three nonspecific DNTs), the hyperperfused area was wider than the lesion observed on the MR scans (Fig. 1). The hyperperfusion included the DNTs and a radiologically normal perilesional area corresponding to cortical dysplasia. In these cases, the intensity of hyperperfusion in this area was significantly higher (up to +58% compared with interictal studies) compared with the hyperperfusion observed in other lesional (e.g., glial tumors, hippocampal sclerosis) or nonlesional epilepsy (data not shown).

Figure 1.

Preoperative magnetic resonance imaging (MRI) (A, B), subtraction of ictal and interictal single-photon emission computed tomography (SPECT) coregistered to MRI (SISCOM) (C–H), and postoperative MRI (I–L) images in case 3 [dysembryoplastic neuroepithelial tumor (DNT) complex form]. The preoperative MRI shows an intracortical temporal external well-marginated hypointense mass on T1-weighted images, with a cystic appearance, without calcification. Cortical dysplasia surrounding the lesion is not evident. SISCOM findings, obtained after early ictal tracer injection, demonstrate an abnormally hyperperfused area (+30 to 46%) wider than anatomic abnormalities on MRI (F–H), corresponding to histopathologically confirmed cortical dysplasia associated with DNT. The postoperative MRI shows the limits of resection in relation to the abnormally hyperperfused area detected by SISCOM (J–L).

In three patients with DNTs without cortical dysplasia (one specific, two nonspecific DNTs), the hyperperfused area was limited to the size of the lesion visualized on the MR scans (Fig. 2).

Figure 2.

Preoperative magnetic resonance imaging (MRI) (A, B), subtraction of ictal and interictal single-photon emission computed tomography (SPECT) coregistered to MRI (SISCOM) (C–H), and postoperative MRI (J–L) images in case 4 [dysembryoplastic neuroepithelial tumor (DNT) without associated focal cortical dysplasia]. Preoperative MRI shows an intracortical hypointense lesion on T1-weighted images, heterogeneous and multicystic, without calcification, located in right temporobasal lobe, associated with a moderate deformity of the adjacent calvarium. SISCOM images, obtained after early ictal tracer injection, show a circumscribed area of hyperperfusion, closely associated with the visualized anatomic abnormalities on MRI. The relative value of hyperperfusion is significantly higher (+30 to 58%) when it coincides with the MRI abnormalities (F–H), and moderate when it corresponds to seizure propagation. The postoperative MRI shows the limits of resection in relation to the abnormally hyperperfused area detected by SISCOM (J–L).

Surgical procedure and postoperative seizure outcome

In five patients (cases 1, 3, 6, 8, and 9), formal anterior temporal lobectomy including the DNT, the amygdala, and the anterior two thirds of the hippocampus was performed, based on the electroclinical and imaging data. The extent of the resection was 3 cm in the left anterior temporal lobe (three patients) and 5 cm in the right temporal lobe (two patients). In three patients (cases 2, 4, and 5), lesionectomy associated with the resection of the adjacent cortex was performed. Resection was stopped at the level of the adjacent sulcus in the left hemisphere (one patient), and in the right hemisphere (two patients). In one patient (case 7), the initial lesionectomy was partial and required further standard temporal lobectomy because of the persistence of mesial temporal lobe seizures.

The mean follow-up period ranged from 10 to 26 months. Postoperatively, all patients were seizure free, and no residual epileptiform activity was detected on EEG monitoring, including the patient with bilateral temporal asynchronous interictal abnormalities. In all cases, neuropsychological investigations showed a clear improvement on postsurgical follow-up.

Neuropathologic data

In one patient (case 1), macroscopic examination of the material after surgery showed a well-circumscribed lesion located within the cortex. A unique specific glioneuronal element was identified, composed of columnar structures made of bundles of axons lined by tumoral oligodendrocytes and surrounded by pale eosinophilic interstitial fluid. There was no involvement of the subcortical white matter. The surrounding cortex was normal, and a diagnosis of simple form of DNT was made.

In three patients (cases 3, 7, and 8), the specific glioneuronal element was associated with a glial nodules made of tumoral oligodendrocytes or astrocytes and foci of cortical dysplasia surrounding the main lesion. Cortical dysplasia was characterized by a loss of normal lamination and the presence of voluminous ectopic neurons into the white matter. In those cases, a diagnosis of complex form of DNT associated with cortical dysplasia was made. In case 7, the lesion had been previously misdiagnosed as pilocytic astrocytoma on the first histopathologic examination after the initial partial lesionectomy.

In the remaining five patients, the tumor lacked the specific glioneuronal element. The histopathologic analysis showed a prominent population of small oligodendroglial cells associated with neurons with variable degree of atypia and small calcifications. A diagnosis of nonspecific form was made. In three of five of those cases, a pattern of cortical dysplasia surrounding the lesion was identified.


In drug-resistant epilepsy, combining, in clinical practice, noninvasive investigations (interictal and ictal video-EEG, interictal and ictal SPECT, and MRI) usually offer sufficient information about epileptogenic zones to make a decision either to proceed with surgery or not. Currently, the only practicable methods to record periictal pathophysiological changes are video-EEG and SPECT. Recently, it using the SISCOM method to interpret SPECT images has been suggested (16,18–22). This method improves the sensitivity and specificity of SPECT images to determine the epileptogenic and propagation zones in intractable focal epilepsy.

The SISCOM results presented in this study demonstrate that the hyperperfusion pattern observed during DNT-related seizures has two characteristics: first, compared with seizures due to other cerebral tumors, all the structural abnormalities observed on MRI, including the cystic component, were hyperperfused; and second, compared with other cases of epilepsy, the perfusion values observed during the seizures were much higher (2 or 3 times more) in the DNT and in associated dysplastic tissue. Those findings could suggest that perfusion changes associated with seizures related to cortical malformation during embryogenesis, such as DNT and focal cortical dysplasia, or both, is not a simple consequence of an increased energy demand related to the ictal status, but could depend on the presence and quantity of the neuronal component within the lesion or the epileptic network. An analogous pathophysiology of increased cerebral perfusion, analyzed by ictal SPECT, due to an increased neuronal population within a lesion, may exist in cases of chronic epilepsy related to other congenital cortical malformations, such as tuberous sclerosis (23).

In our material, we identified histopathologically five cases of nonspecific DNTs associated or not found with cortical dysplasia (Table 1). The recognition of this subgroup of DNTs is crucial from several points of view, particularly (a) from a neurooncology point of view, to discriminate them from glial tumors, and so avoid unnecessary adjuvant radio- or chemotherapy; and (b) from an epileptogenic point of view, because the presence or extent of cortical dysplasia is not identifiable on standard MRI, which is crucial because this area is usually part of the epileptogenic zone.

From a neurooncology point of view, in absence of obvious peculiar histologic criteria, the diagnosis of a nonspecific form of DNT may be considered when both the clinical and neuroradiologic features (particularly with respect to the stability of the size and morphology of lesions) are similar to those of typical DNTs (5). However, making a differential diagnosis between DNTs and glial tumors, particularly low-grade tumors, is often difficult, when based on clinical and neuroradiologic findings (7,8,10,24,25), and histopathologic confirmation is essential. Recently, in a small group of patients, interictal SPECT was used in the presurgical evaluation to better differentiate DNTs from other low-grade gliomas (26). Moreover, it has been suggested that ganglioglioma and DNTs may represent different clinical and morphologic spectra of the same disease process, such as a transitional form (10,27,28), with a close histogenetic relationship (27). Moreover, dysplastic cortical disorganization adjacent to the lesion may be difficult to distinguish from secondary architectural changes observed in infiltrative gliomas (1), and differentiating small neuronal cells from oligodendrocytes often requires ultrastructural examination (10). In our study, we found five cases of nonspecific DNTs, several associated with cortical dysplasia.

From the epileptogenic point of view, experimental studies have demonstrated that cortical dysplasia is strongly associated, in animal models, with an epileptic phenotype, and that a broad spectrum of mechanisms contributed to generate abnormal neural circuitry beyond the epileptogenic region. Decreased inhibition or increased excitation, or both, are responsible for the existence of a wide network of disturbances within the dysplastic cortex and its hyperexcitability (29). Immunocytochemical evidence in surgical specimens suggested that, in cortical dysplasia, disorganization of the cortical architecture and reduced expression of calcium-binding proteins increase the activity of pyramidal excitatory neurons and decrease inhibitory circuits of γ-aminobutyric acid (GABA)ergic interneurons (30), thereby confirming the presence of exuberant excitatory networks that could be modulated by variations in the conductance of GABAA receptors (31). Recently, some authors have reviewed the role, in clinical practice, of malformation during cortical development associated with focal epilepsy, demonstrating that in these forms of lesional epilepsy, epileptogenesis is often widespread because malformed cortex is functionally aberrant, even if still anatomically conserved (32).

From the point of view of surgical treatment, in our series, the degree of resection was established on the basis of clinical, electrophysiologic, morphologic, and SPECT images. The symptomatogenic zone, corresponding to the initial clinical signs of seizures (33) and to areas involved early in discharge propagation (33,34), was wider than structural abnormalities on neuroimaging. Defining the epileptogenic and symptomatogenic zones, in those cases in which MRI shows either no lesion or only a small part of the epileptogenic zone, is essential to achieve a postsurgical seizure-free outcome (33). Interestingly, in our study, one patient was seizure free only after a standard temporal lobectomy, because previously subtotal lesionectomy was insufficient for seizure control. The histologic examination of residual lesion material after surgery revealed the presence of cortical dysplasia. The widespread temporal hyperperfusion observed in the SISCOM study (ictal SPECT was performed after the first surgical treatment) suggests the existence of partially removed cortical dysplasia associated with DNT, and that a residual epileptogenic and symptomatogenic network explains the failure of the first operation.

These preliminary data suggest that SISCOM, used among presurgical investigations in temporal lobe epilepsy related to DNTs, contributes to the detection of cortical dysplasia associated with the tumors (usually corresponding to perilesional normal areas on MRI), and to a better definition of the epileptogenic network. Concordance between the symptomatogenic zone (defined from the medical history and electroclinical data), MRI scans, SISCOM pattern, and complete resection of the epileptic zone is predictive of a good postsurgical outcome.

Acknowledgment: We gratefully acknowledge the contribution of Prof. C. Daumas-Duport (Department of Pathology and Neurologic Surgery, Hopital Sainte Anne, Paris, France) for the revision of pathological specimens. We thank members of the French network of epilepsy surgery for clinical help and Prof. D. Grucker for valuable advice. The assistance of the Epilepsy Unit, MRI, and Nuclear Medicine staff in acquiring data is gratefully acknowledged. We also thank Ms. N. Heider for correcting the English.

This work was supported by a grant from the Hôpitaux Universitaires de Strasbourg and the Université Louis Pasteur.