Presurgical evaluation of refractory temporal lobe epilepsy ...Presurgical evaluation of refractory...

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ORIGINAL ARTICLE Presurgical evaluation of refractory temporal lobe epilepsy: Comparison of MR imaging, PET and ictal SPECT in localization of the epileptogenic substrate q Hassan Kassem a , Fahd El Shiekh b , Ahmed Wafaie c, * , Sherif Abdelfattah c , Hussein Farghaly d , Lamia Afifi e a Department of Radiology, Benha University, Egypt b Department of Radiology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia c Department of Radiology, Cairo University, Egypt d Nuclear Medicine Unit, Assiut University, Egypt e Clinical Neurophysiology Unit, Cairo University, Egypt Received 23 February 2013; accepted 8 April 2013 Available online 9 May 2013 KEYWORDS Refractory temporal lobe epilepsy; MRI; FDG-PET; Ictal SPECT Abstract Purpose: To compare the sensitivities of MRI, FDG-PET and ictal/SPECT in localiza- tion of the epileptogenic substrate in patients with refractory temporal lobe epilepsy. Patients and methods: This study included 137 patients who received surgical treatment for intrac- table epilepsy. MRI, FDGPET and ictal 99m Tc-HMPAO SPECT were retrospectively reviewed regarding their sensitivity in lateralization of the epileptogenic zone compared to video/EEG, path- ological results and surgical outcome. Results: 104 MR-positive and 33 MR-negative patients were enrolled. In the MR-positive group, MRI, PET and ictal/SPECT were concordant to video/EEG in 72%, 83% and 73%, respectively. When compared to pathological diagnosis, they correctly lateralized the epileptogenic zone in 70%, 87%, and 73%, respectively. In patients with good surgical outcome, they correctly localized the epileptogenic zone in 79%, 88%, and 78%, respectively. In the MR-negative group, PET and q Presented as an educational exhibit in the 98th Scientific Assembly and Annual Meeting of the Radiological Society of North America (LL-NRE2566), November 25–30, 2012, McCormick Place, Chicago, USA. * Corresponding author. E-mail address: [email protected] (A. Wafaie). Peer review under responsibility of Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier The Egyptian Journal of Radiology and Nuclear Medicine (2013) 44, 641–649 Egyptian Society of Radiology and Nuclear Medicine The Egyptian Journal of Radiology and Nuclear Medicine www.elsevier.com/locate/ejrnm www.sciencedirect.com 0378-603X Ó 2013 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Radiology and Nuclear Medicine. http://dx.doi.org/10.1016/j.ejrnm.2013.04.003

Transcript of Presurgical evaluation of refractory temporal lobe epilepsy ...Presurgical evaluation of refractory...

Page 1: Presurgical evaluation of refractory temporal lobe epilepsy ...Presurgical evaluation of refractory temporal lobe epilepsy: Comparison of MR imaging, PET and ictal SPECT in localization

The Egyptian Journal of Radiology and Nuclear Medicine (2013) 44, 641–649

Egyptian Society of Radiology and Nuclear Medicine

The Egyptian Journal of Radiology andNuclearMedicine

www.elsevier.com/locate/ejrnmwww.sciencedirect.com

ORIGINAL ARTICLE

Presurgical evaluation of refractory temporal lobe epilepsy:

Comparison of MR imaging, PET and ictal SPECT

in localization of the epileptogenic substrateq

Hassan Kassema, Fahd El Shiekh

b, Ahmed Wafaie

c,*, Sherif Abdelfattahc,

Hussein Farghaly d, Lamia Afifi e

a Department of Radiology, Benha University, Egyptb Department of Radiology, Prince Sultan Military Medical City, Riyadh, Saudi Arabiac Department of Radiology, Cairo University, Egyptd Nuclear Medicine Unit, Assiut University, Egypte Clinical Neurophysiology Unit, Cairo University, Egypt

Received 23 February 2013; accepted 8 April 2013

Available online 9 May 2013

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KEYWORDS

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MRI;

FDG-PET;

Ictal SPECT

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Corresponding author.mail address: a_wafaie@yah

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Abstract Purpose: To compare the sensitivities of MRI, FDG-PET and ictal/SPECT in localiza-

tion of the epileptogenic substrate in patients with refractory temporal lobe epilepsy.

Patients and methods: This study included 137 patients who received surgical treatment for intrac-

table epilepsy. MRI, FDGPET and ictal 99mTc-HMPAO SPECT were retrospectively reviewed

regarding their sensitivity in lateralization of the epileptogenic zone compared to video/EEG, path-

ological results and surgical outcome.

Results: 104 MR-positive and 33 MR-negative patients were enrolled. In the MR-positive group,

MRI, PET and ictal/SPECT were concordant to video/EEG in 72%, 83% and 73%, respectively.

When compared to pathological diagnosis, they correctly lateralized the epileptogenic zone in 70%,

87%, and 73%, respectively. In patients with good surgical outcome, they correctly localized the

epileptogenic zone in 79%, 88%, and 78%, respectively. In the MR-negative group, PET and

the 98th Scientific Assembly

al Society of North America

, McCormick Place, Chicago,

A. Wafaie).

tian Society of Radiology and

g by Elsevier

ing by Elsevier B.V. on behalf of Egyptian Society of Radiology and Nuclear Medicine.

4.003

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642 H. Kassem et al.

ictal/SPECT were concordant with video/EEG in 82% and 58%, respectively and matching with

pathological diagnosis in 85% and 56%, respectively.

Conclusion: PET is the most sensitive method in lateralization of the epileptogenic substrate. The

use of MRI, PET and ictal/SPECT as a multimodality approach improves lateralization of the

affected zone particularly in cases with negative MR findings and distinguishes patients who will

benefit from surgery.

� 2013 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Radiology and Nuclear

Medicine.

1. Introduction

Surgery for treatment of epilepsy has emerged as a worldwide

established option for treatment of patients with seizure that isrefractory to antiepileptic drug management. In patients withrefractory epilepsy, neuroimaging is crucial for precisely iden-

tifying epileptogenic foci that are potentially amenable to sur-gical resection for possible cure (1). Electroencephalogram(EEG) remains the most powerful tool for delineating the epi-

leptogenic zone and is the primary tool in the selection andevaluation of presurgical candidates at most institutions (2).In the clinical setting, structural MR imaging remains the fun-damental neuroimaging technique for identifying a lesion that

could be responsible for the epilepsy (3). Functional radionu-clide imaging including PET and ictal SPECT or advancedmagnetic resonance imaging techniques can provide comple-

mentary information when an epileptogenic substrate is notidentified or in the presence of non-concordant clinical andstructural findings (4).

The objective of this study is to compare the sensitivity ofMR imaging, FDG-PET, and ictal 99mTc-HMPAO SPECTin pre-operative localization of the epileptogenic zone in

patients with refractory temporal lobe epilepsy in bothpediatric and adult patient groups using video/EEG andpathological findings as standards of reference. We alsocompared the relationship between the concordance rates of

these imaging modalities with the post-surgical outcome.

2. Patients and methods

Our study included 137 patients who received surgical treat-ment for their medically intractable epilepsy during the periodfrom September 2006 through February 2011. The presurgical

diagnosis of temporal lobe epilepsy was made by clinical his-tory, seizure semiology and video/EEG monitoring and waspathologically confirmed after surgery. The patients were 86

males and 51 females with an age range at the time of surgeryof 2 to 67 years (mean, 29 years).

Video EEG was recorded in the special epilepsy ward using

a 24 hour video-monitoring system. Scalp EEG was recordedusing an EEG cap utilizing the 10–20 electrode placementsystem. Data were recorded using a Nihon Kohden EEGmachine. Ictal EEG changes, MRI, FDG-PET, and ictal99mTc-HMPAO SPECT were retrospectively reviewedregarding their sensitivity in localization of the affected zone.

2.1. Structural high-resolution MR imaging

Structural high-resolution MR imaging was performed usingG.E signa LX 1.5T and GE signa HDxc 3.0T machines with

standard head coil. Our protocol started with the examination

of the whole brain using conventional spin-echo T1-weightedsagittal and axial images with axial FLAIR, DWI and T2-

weighted images using 3 mm section thickness and 1 mmgap. Then dedicated sequences for the temporal lobes were ob-tained including coronal T1 3D SPGR, T2 IR, FLAIR and T2-

weighted images perpendicular to the long axis of the hippo-campus using 1.5 mm slice thickness sections. T1-weightedgadolinium-enhanced images were performed in selected casessuch as tumors.

2.2. Positron emission tomography

PET was performed with an injection of 2–10 mCi of 18F fluo-

rodeoxyglucose (FDG) during the interictal period on a Gem-ini Philips time of flight scanner. Patients were either sedated ifuncooperative or if cooperative asked to lie still with their eyes

closed in a quiet dimly lit room. The patients were examined30–40 min after injection. The acquisition time was 10–20 min. Axial and coronal images were reconstructed with a

Shepp–Legon filter. The criterion of abnormality was the pres-ence of asymmetrical temporal lobe decrease in FDG uptake(15% or more).

2.3. Ictal single photon emission CT

Ictal Technetium (99mTc) Hexamethyl propyleneamine oxime(HMPAO) was performed using a dual-head Infinia Gamma

camera GE Healthcare equipped with low-energy ultra high-resolution (LEUHR) collimator. The radiopharmaceuticalwas injected intravenously within 30 s after the onset of seizure

in a dose of 7.4–11.1 MBq/kg for children and 740 Mbq foradults. Data acquisition was started 30–90 min after the sei-zure activity ceased. Sixty-four views, each registered over40 s were recorded in a 128 · 128 matrix with pixel size of

2.9 · 2.9 mm. Transaxial tomograms were reconstructed usinga Butterworth filter generating coronal and sagittal slices. Thein-plane resolution of the reconstructed images was 11 mm

FWHM and section thickness was approximately 5–8 mm.For the ictal SPECT, the area of hyperperfusion relative tothe remaining regions was considered as the epileptogenic

zone.

2.4. Criteria for correct localization

Correct localization of the epileptogenic substrate was consid-ered when the abnormal finding in MR imaging, PET or ictalSPECT matched the video/EEG results, the operative site andthe location of histopathological abnormality. Correct lateral-

ization by PET or ictal SPECT was also interpreted when thediffuse abnormality detected by these imaging methods wasoverlapped with the operative site.

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Presurgical evaluation of refractory temporal lobe epilepsy: Comparison of MR imaging, PET and ictal SPECT 643

Concordance was considered when MRI, PET, or ictalSPECT localized the epileptogenic zone in the same area ofabnormality compared to each other and compared to video/

EEG, and histopathological findings. Non-concordance wasconsidered when the abnormal finding detected by the imagingmethod was not matching compared with one another and

with pathological findings.All the patients were followed up for 12 months or more

after surgery to assess the relationship between the concor-

dance rates of each imaging modality and the post-surgicaloutcome. The concordance or non-concordance was deter-mined according to whether the preoperative localizationwas matching the operative site or not. The Engel’s four cate-

gories system was used to assess the post-surgical outcome (5).It includes; Class I (seizure-free) indicates an absence of seizureactivity since surgery, regardless of medication. Class II indi-

cates rare seizures; that is, a few in a year. Class III indicatesworthwhile improvement, meaning at least a 75% improve-ment in seizure frequency compared with preoperative status.

Class IV denotes no worthwhile improvement. In our study,good post-surgical outcome was considered in patients who re-mained seizure-free or with few seizures for 12 months or more

after surgery (Engel’s class I and II).

Fig. 1 Concordance among the MRI, ictal SPECT and PET in a

57 year old female with refractory right temporal lobe epilepsy.

(A) Ictal SPECT showed hyperperfusion of the right temporal

lobe. (B) Interictal FDG-PET showed significant hypo metabolism

in the right temporal lobe. (C) and (D) Coronal FLAIR and T2-

weighted MR image showed small sized right hippocampus

compared to the left one with hyperintensity and loss of the

normal alternating gray and white matter internal architecture

(arrows). After anterior temporal lobectomy, the pathological

diagnosis was right hippocampal sclerosis. Engel’s outcome was

class I.

3. Results

From the total 137 patients with temporal lobe epilepsy in-cluded in this study, 104 patients showed positive findings onMR-imaging (MR-positive group) and 33 cases showed nodefinite lesions on MR imaging (MR-negative group).

3.1. MR-positive group

This group included patients in whom preoperative MRI de-

tected an apparent temporal lobe lesion whether the lesion isunilateral or bilateral and whether involving the mesial (hippo-campus, parahippocampal gyrus and amygdala) or lateral

(neocortex or lateral cortex) temporal lobe structures. Themost numerous pathology was hippocampal sclerosis (65%).Developmental malformations including microdysgenesis and

focal cortical dysplasia were the second most frequent pathol-ogy (16%). Epileptogenic tumors were found in 12% of casesof this group (dysembryoplastic neuroepithelial tumor(DNET), 5%, ganglioglioma, 4%, low grade astrocytoma,

3%). Gliosis (post-ischemic or post-traumatic) was the leastfrequent lesions (7%) found in this group.

Compared to video/EEG as a first standard of reference,

MR imaging, PET and ictal SPECT were concordant in72%, 85% and 73% of cases, respectively. The three modali-ties were concordant to each other and matching the abnormal

video/EEG findings in 58% of cases (Figs. 1 and 2). The non-concordance among the three imaging methods was found in42% of cases (Figs. 3 and 4). When using the pathological find-

ings as a second standard of reference, MR imaging, PET andictal SPECT correctly localized the epileptogenic substrate in70%, 87% and 73% of cases, respectively.

The post-surgical outcome was considered the third stan-

dard of reference using the Engel’s outcome classification sys-tem (5). Engel’s class I (seizure-free for 12 months or moreregardless of the medication) and class II (rare seizure; that

is, few seizures in a year) were considered as a good outcome.

Of the MR-positive group, 78 patients (75%) had good out-come. MR imaging, PET and ictal SPECT correctly localized

the lesions in 79%, 88% and 78% of cases, respectively.MRI, PET and ictal SPECT were concordant together in60% of the cases of this subgroup (Table 1).

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Fig. 2 Concordance among the MRI, ictal SPECT and PET in a 15 year old female with right TLE. (A) Ictal SPECT showed

hyperperfusion of the right temporal lobe. (B) Interictal FDG-PET showed significant hypometabolism in the right temporal lobe. (C)

Coronal IR MR image showed right mesial temporal lobe cortically-based hypointense lesion with solid and cystic components (arrow).

The lesion was not enhancing in postcontrast images (not included). Histopathological examination after surgical resection revealed right

temporal ganglioglioma with associated FCD. The three modalities were concordant with pathology in lateralization of the epileptogenic

zone.

Fig. 3 Non-concordance among the MRI, ictal SPECT and PET in a 3 year-old boy. Ictal activity was shown in the left temporal area

on video/EEG. (A) CoronalT2-weighted MR images showed abnormal high signal intensity involving the left parahippocampal and

fusiform gyri, with T2 hyperintense area in the white matter and focal blurring of the gray-white matter junction (arrow). (B) Ictal SPECT

showed hyper-perfusion in the right temporo-parietal region and in the medio-inferior aspect of the left temporal lobe. (C) Interictal FDG-

PET showed hypometabolism in the left temporal lobe. Pathological evaluation after operation demonstrated type IIB left Focal Cortical

Dysplasia (FCD). Engel’s outcome was class II. This case showed concordance of MRI and PET with video/EEG and pathology and

failure of ictal SPECT to lateralize the epileptogenic substrate.

644 H. Kassem et al.

3.2. MR-negative group

This group included 33 patients (non-lesional group). The MR

imaging was apparently normal reported by two neuroradiol-

ogists (Fig. 5). The sensitivity of PET and ictal SPECT inlocalization of the epileptogenic zone was 82% and 58%,respectively compared to video/EEG whereas the two modali-

ties were concordant to pathological diagnosis in 85% and

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Fig. 4 Non-concordance among the MRI, PET and ictal SPECT in a female patient, 48 years old with intractable left complex partial

seizures. Video/EEG lateralized the ictal activity in the left temporal lobe. (A) Coronal T2-weighted image showed dilatation of the left

temporal horn with questionable hyperintensity of the left hippocampus. Left mesial temporal sclerosis was suspected. (B) Axial FLAIR

showed left insular cortex hyperintense signal with atrophy of the left caudate nucleus together with ex vacuo dilatation of the left frontal

horn (arrow). (C) Interictal FDG-PET showed left basal ganglia hypometabolism. (D) Ictal SPECT showed hyperperfusion on the left

frontal and temporal lobes. Because the localization was inconclusive and not adequate for precise surgery, invasive EEG was performed

showing ictal activity on the left insular cortex. After operation, the pathological diagnosis was left insular gliosis. Engel’s outcome was

class III.

Presurgical evaluation of refractory temporal lobe epilepsy: Comparison of MR imaging, PET and ictal SPECT 645

56% of cases, respectively. Twenty patients (60%) of this

group had good surgical outcome. PET correctly lateralizedthe abnormality in 80% of the cases of this group versus75% by ictal SPECT. The combination of both modalities in-

creased sensitivity to 100% (Table 2). The abnormalitiesapparently missed by MR imaging and their zone correctly de-picted by PET and ictal SPECT were as follows: cortical dys-plasia (n= 8), microdysgenesis (n= 19), hippocampal

sclerosis (n= 3), and focal neuronal loss (n= 3).

4. Discussion

In the management of temporal lobe epilepsy, exact lateraliza-tion/localization of seizure focus with a noninvasive study iscrucial, because surgical resection of the epileptogenic lesionresults in good outcome (Engel class I or II) and a failure to

lateralize the focus with noninvasive examination may leadto an invasive study or to additional surgery for placementof intracranial electrodes, which may have potential risks (6).

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Table 1 MR-positive group (n= 104): Concordance rates compared to the three standards of reference.

Imaging method Concordance rates

1st Standard of reference

(Video/EEG) (%)

2nd Standard of reference

(pathological results) (%)

3rd standard of reference

(surgical outcome) (%)

MR imaging 72 70 79

FDG-PET 85 87 88

Ictal SPECT 73 73 78

646 H. Kassem et al.

Electroencephalogram (EEG) remains after 80 years sinceits first conception by Hans Berger, the most powerful tool

in our arsenal for delineating the epilepsy and is the primarytool in the selection and evaluation of presurgical candidatesat most institutions (2). However clear focus localization, espe-

cially in temporomesial structures of patients with TLE, is stilla difficult task in which extensive video EEG monitoring issuccessful in 60–90% of cases (7).

Functional and structural neuroimaging techniques areincreasingly indispensable in the evaluation of epileptic pa-tients for localization of the epileptic area as well as for under-standing pathophysiology, propagation, and neurochemical

correlates of chronic epilepsy (8).MR imaging remains the method of choice for depicting

gross structural lesions in the brain. However in our study even

when using state-of-the-art protocols and using high resolution3.0T machine in some cases, 24% of cases (33/137) remainedwithout apparent lesion on MRI (MR-negative group).

Although this ratio is less than other previous studies (9), itis still significant. In the cases where MRI shows no obviouslesions, PET and SPECT play a complementary role in thelocalization or lateralization of the epileptogenic focus and

minimize the need for invasive EEG monitoring.Only few studies comparing MRI, PET, and ictal SPECT in

localizing the epileptogenic foci have been reported (8,10,11),

presumably due to the limited availability of these techniques.To our knowledge, no recent study has been published com-paring these modalities in the temporal lobe substrate detec-

tion after the technical advancement of the three modalitiesand no recent reports available compared the 3.0T MR imageswith PET and ictal SPECT as regards the epileptogenic tempo-

ral zone detection.Spencer (8) in his review of temporal lobe epilepsy found

that the highest sensitivity was obtained with ictal SPECT(90%), the lowest sensitivity with MR imaging (55%) and

intermediate sensitivity with PET (84%) when he used EEGas a standard of reference. However the technical advancementsince the study conducted by Spencer has improved the detec-

tion rate of pathological lesions. In our study, the overall cor-rect localization rate of the epileptogenic substrate was 72%with MR imaging, 85% with PET, and 73% by ictal SPECT.

This means that the highest sensitivity was achieved by PETwhereas ictal SPECT and MRI were nearly comparable. Thiswas also reported by Hyung et al. (10) who found that PET

showed the highest sensitivity for detection of both temporaland extratemporal epileptogenic lesions.

Good outcomes (Engel’s class I and II) after surgery fortemporal lobe epilepsy have been reported in approximately

70% to 90% of cases (12,13). In the present study, the correctlocalization rate of MR imaging in patients with good post-surgical outcome (79%) was higher than that for the total pa-

tients compared to video/EEG (72%). In those patients withfavorable postsurgical outcome, PET detected the hypometab-

olism zone in 88% of cases compared to the area of hyperper-fusion correctly localized by ictal SPECT in 87% of cases. Inpatients with normal MRI (MR-negative group) who had

good surgical outcomes, the correct localization rates of theseizure focus by PET (80%) and ictal SPECT (75%) remainedgood. These findings indicated that PET and ictal SPECT in

temporal lobe epilepsy show relatively comparable correctlocalization rates regardless the lesion detected by MRI ornot. However detection of the lesion by MR imaging is associ-ated with a better surgical outcome. This reflects that focal

abnormalities, such as tumors, are well revealed by MR imag-ing and can be completely removed. Therefore, outcomes asso-ciated with focal abnormalities such as tumors will be better

than those associated with diffuse or multifocal abnormalities,such as neuronal migration disorder or gliosis, which cannotbe resected entirely.

In our study, when MRI was compared to video/EEG inlocalization of the epileptogenic substrate, 72% concordancerate was found whereas the non-concordance rate was about28%. The latter rate is considered significant and showed the

necessity of using multiple imaging techniques in order to ob-tain accurate pre-surgical evaluation. The concordance rate ofPET and ictal SPECT was 85%, and 73% of cases, respec-

tively. The three modalities were concordant to each otherand matching the abnormal video/EEG findings in 58% ofcases. This means that on using the different imaging modali-

ties in our study, the non-concordance rate remained high(42%). This ratio coincides with what has been reported byHyung et. al (10) who found the non-concordance rate as

much as 30–40% of their patients.The discrepancies among the different imaging techniques

may be explained by the fact that they measure different as-pects of the epileptic process; that is, MR imaging depicts only

gross anatomic alterations associated with epilepsy whereasPET displays the cerebral metabolism and ictal SPECT mea-sures the cerebral perfusion (14). MR imaging and PET have

an advantage in visualizing the whole brain; they not only de-pict the lesion in the medial temporal lobe but can also showabnormalities in other regions, such as an asymmetric, small,

ipsilateral mamillary body and fornix on MR images in a pa-tient with hippocampal sclerosis (15) and an asymmetric hypo-metabolism of the thalamus on PET scans in a patient with

mesial temporal lobe epilepsy (16).In seizure-onset focus detection, the anatomical/pathologi-

cal definition of the organic lesion is the most obvious on MRimages. PET has the unique ability to image cerebral metabo-

lism but is virtually limited to the interictal state, because ittakes approximately 1 hour for the radiotracer to enter thecells to be metabolized and to be distributed throughout the

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Fig. 5 Concordance between PET and ictal SPECT in patient with normal MRI. Male patient, 67 years old with right temporal lobe

epilepsy lateralized by EEG. (A) Oblique coronal FLAIR and spin-echo T2-weighted MR image showed no obvious abnormality. (B)

Interictal FDG-PET showed hypometabolism in the right temporal lobe. (C) Ictal SPECT shows hyperperfusion in right temporal lobe.

Pre-operative subdural invasive EEG was performed showing the epileptogenic focus in the right temporal lobe. After right anterior

temporal lobectomy, pathological diagnosis was right hippocampal sclerosis. The patient remained seizure-free on 12 month follow-up.

Table 2 MR-negative group (n= 33): Concordance rates compared to the three standards of reference.

Imaging method Concordance rates

1st Standard of reference

(Video/EEG) (%)

2nd Standard of reference

(pathological results) (%)

3rd standard of reference

(surgical outcome) (%)

FDG-PET 82 85 80

Ictal SPECT 58 56 75

Presurgical evaluation of refractory temporal lobe epilepsy: Comparison of MR imaging, PET and ictal SPECT 647

brain tissue. This time is too long to image the relatively shortictal state (10). SPECT, on the other hand, is used to assess the

cerebral blood flow changes not only in the interictal state butalso during the ictal period, as the radiotracer injected duringthe ictal state is distributed throughout the brain tissue within

1 min and remains radioactive in the brain tissue after cessa-tion of seizure activity without significant redistribution (17).

In patients with normal MR imaging, PET was superior toictal SPECT in lateralizing the epileptogenic substrate (85%versus 58%) when video/EEG was used as a standard of refer-

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648 H. Kassem et al.

ence. The sensitivity of ictal SPECT in this group of patients isconsidered relatively low. This could be explained in our studyby the relatively late injection of the radiotracer. The timing of

injection of the radiotracer is very critical in ictal SPECT to de-tect the seizure-onset zone. If the radiotracer is injected lateduring the seizure or after the seizure is over, isoperfusion or

even hypoperfusion may be seen in the responsible area (18).Because the spread of ictal discharges to other areas of thebrain may occur within seconds of seizure onset, the SPECT

scan, even with injection approximately 1 min after the onsetof a seizure, may not indicate the site of onset (10).

The sensitivity of MRI, PET and ictal SPECT in epilepto-genic zone detection (72%, 85%, and 73%, respectively) com-

pared to video/EEG was relatively high in our study comparedwith some of the previous studies. In the series of Sung et al,(19) MR imaging, PET, and ictal SPECT localized the epilep-

togenic foci correctly in 60%, 78%, and 70% of patients,respectively. In Hyung et al. series (10) the sensitivity of thethree modalities was 58%, 68%, and 58%.of cases, respec-

tively. This discrepancy in sensitivity between those previousstudies and our study is likely due to the technical advancesof the imaging methods since these studies have been published

particularly the technical maturation of using the 3.0T ma-chine in cases of epilepsy which certainly improves the locali-zation ability of MRI to the epileptogenic substrate.

Despite the use of high resolution MRI protocols and using

the 3.0T machine, 24% of cases (33/137) showed no abnormalfindings on MRI. Cortical dysplasia and microdysgenesis rep-resented the majority of the pathological substrates missed by

MRI in our study. These results reflect a relative insensitivityof MR imaging to neuronal migration disorder, especially incases of mild dysplasia. Patients with mild to moderate dyspla-

sia have a tendency to show subtle or unremarkable findingson MRI (20). In these mild degree lesions, PET was more sen-sitive than ictal SPECT in localizing the seizure-onset zone

(85% versus 56% compared to pathology). These results arealso consistent with a previous review of literature describingthat half the patients with normal MR imaging in cases of neu-ronal migration disorder had abnormal PET and SPECT find-

ings (21). These findings suggest the role of PET and ictalSPECT as complementary tools to MR imaging in cases withnegative MR imaging findings.

Precise localization and removal of the epileptogenic focusis the ultimate treatment goal in patients with refractory tem-poral lobe epilepsy. Ideally, the probability of cutting the pri-

mary seizure focus out of the brain must approach 100%before an irreversible lobectomy is performed. However, untilnow, no single diagnostic test has proved sufficient in localiz-ing the site to be surgically resected (19).

So far, no single technique appears clearly superior overallto any of the others. Combination of localizing tests support-ing clinical and scalp EEG findings should allow more patients

to skip, for example, invasive intracranial EEG (22).In our opinion, if the MRI detects definite unilateral epilep-

togenic abnormality, PET and ictal SPECT will be further

complementary diagnostic options for correct localization. Ifthe three modalities are concordant to each other and match-ing with video EEG, our data suggest that no invasive sub-

dural EEG is needed as it usually provides no additionalinformation and at the same time carries the risk of an invasiveprocedure. On the other hand, if the MR imaging is normal(MR-non-lesional group) or if there is non-concordance be-

tween MRI and video/EEG, complementary functional studiesby PET and ictal SPECT are indicated for the localization pro-cess. If the two imaging methods (PET and ictal SPECT) are

concordant to each other and matching with video/EEG, noinvasive intracranial EEG might be needed for localizationinformation. But if the localization is still inconclusive and

not adequate for precise surgery, or if there is still some dis-crepancy among the multiple techniques, an invasive study,usually with subdural electrodes, should be performed.

5. Conclusion

PET is the most sensitive method in lateralization of the epi-

leptogenic zone. Although PET and ictal SPECT are more sen-sitive than MRI in lateralization of the epileptogenic lesions,the detection of abnormality by MRI is associated with good

post-surgical outcome. The use of MRI, PET and ictal SPECTas a multimodality approach improves lateralization of the af-fected zone particularly in cases of negative MR finding anddistinguish patients who will benefit from surgery.

References

(1) Rastogi Sachin, Lee Christopher, Salamon Noriko. Neuroimag-

ing in pediatric epilepsy: a multimodality approach. Radiograph-

ics 2008;28:1079–95.

(2) Jeong TK, Sung JB, Keum OC, Yoon JL, Hae JP, et al.

Comparison of various imaging modalities in localization of

epileptogenic lesion using epilepsy surgery outcome in pediatric

patients.. Seizure: European J Epilepsy 2009;18:504–10.

(3) Winjaja Elysa, Raybaud Charles. Advances in neuroimaging in

patients with epilepsy. Neurosurg Focus 2008;25(3):1–11.

(4) Lai Vincent, Mak Henry, Yung Ada, Ho WY, Hung KN.

Neuroimaging techniques in epilepsy. Hong Kong Med J

2010;16:292–8.

(5) Engel Jr J. Outcome with respect to seizures. In: Surgical

treatment of the epilepsies. New York: Raven; 1987.

(6) Anderson F. Identification of candidates for surgical treatment of

epilepsies. New York: Raven; 1987, pp. 51–70.

(7) Pataraia E, Lurger S, Series W, et al. Ictal scalp EEG in

unilateral mesial temporal lobe epilepsy. Epilepsia

1998;39:608–14.

(8) Spencer SS. The relative contributions of MRI SPECT and PET

imaging in epilepsy. Epilepsia 1994;35(Suppl. 6):S27–89.

(9) Van PW, Connelly A, Johnson CL, et al. The amygdale and

intractable temporal lobe epilepsy: a quantitative magnetic

resonance imaging study. Neurology 1996;47:1021–31.

(10) Won Hyung Jin, Chang Kee-Hyun, Cheon Jung-Eun, et al.

Comparison of MR imaging with PET and ictal SPECT in 118

patients with intractable epilepsy. AJNR 1999;20:593–9.

(11) Coubes P, Awad IA, Antar M, et al. Comparison and spatial

correlation of interictal HMPAO-SPECT and FDG-PET in

intractable temporal lobe epilepsy. Neurol Res 1993;15:160–7.

(12) Hardiman O, Burke T, Phillips J, et al. Microdysgenesis in

resected temporal neocortex: incidence and clinical significance in

focal epilepsy. Neurology 1988;38:1041–7.

(13) Feindel W, Rasmussen T. Temporal lobectomy with amygdalec-

tomy and minimal hippocampal resection: review of 100 cases.

Can J Neurol Sci 1991;18(Suppl. 4):603–5.

(14) Park Un-Won, Chang Kee-Hyun, Kim Hong-Dae, et al. Later-

alizing ability of single-voxel proton MR spectroscopy in hippo-

campal sclerosis: comparison with MR imaging and positron

emission tomography. AJNR 2001;22:625–31.

(15) Kim JH, Tien RD, Felsberg GJ, Osumi AK, Lee N. Clinical

significance of asymmetry of the fornix and mamillary body on

Page 9: Presurgical evaluation of refractory temporal lobe epilepsy ...Presurgical evaluation of refractory temporal lobe epilepsy: Comparison of MR imaging, PET and ictal SPECT in localization

Presurgical evaluation of refractory temporal lobe epilepsy: Comparison of MR imaging, PET and ictal SPECT 649

MR in hippocampal sclerosis. AJNR Am J Neuroradiol

1995;16:509–15.

(16) Rausch R, Henry TR, Ary CM, et al. Asymmetric interictal

glucose hypometabolism and cognitive performance in epileptic

patients. Arch Neurol 1994;51:139–44.

(17) Nagata T, Tanaka F, Yonekura Y, et al. Limited value of

interictal brain perfusion SPECT for detection of epileptic foci:

high resolution SPECT studies in comparison with FDG-PET.

Ann Nucl Med 1995;9:59–63.

(18) Berkovic SF, Mcintodh AM, Kainins RM, et al. Preoperative

MRI predicts the outcome of temporal lobectomy: an actuarial

analysis. Neurology 1995;44:1358–63.

(19) Hwanga Sung-IL, Kima Jae Hyoung, Parka Sun Won. Compar-

ative analysis of MR imaging, positron emission tomography, and

ictal single-photon emission CT in patients with neocortical

epilepsy. AJNR 2001;22:937–46.

(20) Mischel PS, Nguyen LP, Vinters HV. Cerebral cortical dysplasia

associated with pediatric epilepsy. Review of neuropathologic

features and proposal for a grading system. J Neuropathol Exp

Neurol 1995;54:137–53.

(21) Spencer SS, Theodore WH, Berkovic SF. Clinical applications:

MRI, SPECT, and PET. Magn Reson Imaging 1995;13:

1119–24.

(22) Doelken MT, Richter G, Stefan H, et al. Multimodal coregis-

tration in patients with temporal lobe epilepsy––results of

different imaging modalities in lateralization of the affected

hemisphere in MR imaging positive and negative subgroups.

AJNR March 2007;28:449–54.