Intracranial EEG versus flumazenil and glucose PET in children with extratemporal lobe epilepsy

OBJECTIVE: To compare abnormalities determined in 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and [11C]flumazenil (FMZ) PET images with intracranial EEG data in patients with extratemporal lobe epilepsy. BACKGROUND: Although PET studies with FDG and FMZ are being used clinically to localize epileptogenic regions in patients with refractory epilepsy, the electrophysiologic significance of the identified PET abnormalities remains poorly understood. METHODS: We studied 10 patients, mostly children (4 boys, 6 girls, aged 2 to 19 years; mean age, 11 years), who underwent FDG and FMZ PET scans, intracranial EEG monitoring, and cortical resection for intractable epilepsy. EEG electrode positions relative to the brain surface were determined from MRI image volumes. Cortical areas of abnormal glucose metabolism or FMZ binding were determined objectively based on asymmetry measures derived from homotopic cortical areas at three asymmetry thresholds. PET data were then coregistered with the MRI and overlaid on the MRI surface. A receiver operating characteristics (ROC) analysis was performed to determine the specificity and sensitivity of PET-defined abnormalities against the gold standard of intracranial EEG data. RESULTS: FMZ PET detected at least part of the seizure onset zone in all subjects, whereas FDG PET failed to detect the seizure onset region in two of 10 patients. The area under the ROC curves was higher for FMZ than FDG PET for both seizure onset (p = 0.01) and frequent interictal spiking (p = 0.04). Both FMZ and FDG PET showed poor performance for detection of rapid seizure spread (area under the ROC curve not significantly different from 0.5). CONCLUSIONS: [11C]flumazenil (FMZ) PET is significantly more sensitive than 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET for the detection of cortical regions of seizure onset and frequent spiking in patients with extratemporal lobe epilepsy, whereas both FDG and FMZ PET show low sensitivity in the detection of cortical areas of rapid seizure spread. The application of PET, in particular FMZ PET, in guiding subdural electrode placement in refractory extratemporal lobe epilepsy will enhance coverage of the epileptogenic zone.     

Relationship of flumazenil and glucose PET abnormalities to neocortical epilepsy surgery outcome.

BACKGROUND: Cortical areas showing abnormal glucose metabolism and [(11)C]flumazenil (FMZ) binding are commonly seen on PET scans of patients with intractable partial epilepsy, but it is unclear whether these must be totally resected to achieve seizure control. OBJECTIVE: To analyze whether the extent of cortex showing 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) or FMZ PET abnormalities correlates with the outcome of resective epilepsy surgery. METHODS: Cortical FDG and FMZ PET abnormalities in 15 young patients (mean age, 12.2 +/- 7.0 years) with intractable partial epilepsy of neocortical origin were marked as regions with abnormal asymmetry using an objective semiautomated software package. These marked regions were then projected and measured on the brain surface reconstructed from the coregistered high-resolution MRI. Following cortical resection, the size of nonresected cortex with preoperative PET abnormalities was also measured (calculated separately for marked areas in the lobe of seizure onset as defined by long-term video EEG monitoring, and in remote cortical areas). Extent of preoperative PET abnormalities and postoperative nonresected cortex abnormalities on PET were correlated with outcome scores. RESULTS: Large preoperative FMZ PET abnormalities were associated with poor outcome (r = 0.57; p = 0.025). Larger areas of nonresected cortex with preoperative FMZ PET abnormalities in the lobe of seizure onset were also associated with worse outcome in the whole group (r = 0.66; p = 0.007) as well as in patients with extratemporal resection (r = 0.73; p = 0.007), and in those with no lesion on MRI (r = 0.60; p = 0.049). Patients with seizure-free outcome had significantly smaller nonresected cortex with preoperative FMZ PET abnormalities than those who continued to have seizures (p = 0.022). No significant correlations between nonresected FDG PET abnormalities and surgical outcome were found. CONCLUSIONS: Extensive cortical abnormalities on FMZ PET predict poor outcome in neocortical epilepsy surgery. Resection of FMZ abnormalities in the lobe of seizure onset is associated with excellent outcome even in the absence of a structural lesion. In contrast, although FDG PET abnormalities regionalized the epileptogenic area, their size was not related to the extent of epileptogenic tissue to be removed.     

Electroclinical correlates of flumazenil and fluorodeoxyglucose PET abnormalities in lesional epilepsy

OBJECTIVE: To analyze the clinical utility of [11C]flumazenil (FMZ) PET to detect perilesional and remote cortical areas of abnormal benzodiazepine receptor binding in relation to MRI, 2-deoxy-2-[18F]fluoro-d-glucose (FDG) PET, and electrocorticographic (ECoG) findings as well as clinical characteristics of the epilepsy in epileptic patients with brain lesion. BACKGROUND: The success of resective surgery in patients with medically intractable epilepsy and brain lesion depends not only on removal of the lesion itself but also on the reliable presurgical delineation of the epileptic cortex that commonly extends beyond it. PET could provide a noninvasive identification of such epileptogenic areas. METHODS: Seventeen patients underwent high resolution MRI, FDG and FMZ PET, and presurgical EEG evaluation, including chronic intracranial ECoG monitoring or intraoperative ECoG. Regional cortical FDG/FMZ PET abnormalities were defined on partial volume-corrected PET images using an objective method based on a semiautomated definition of areas with abnormal asymmetry. Structural lesions were defined on coregistered MRI. The marked PET abnormalities visualized on three-dimensional cortical surface were compared with each other, to the extent of MRI-defined lesion, as well as to ECoG findings. RESULTS: The mean surface extent of FMZ PET abnormalities was significantly larger than the corresponding structural lesions, but it was significantly smaller than areas of glucose hypometabolism. The size of perilesional FDG PET abnormalities showed a correlation with the lifetime number of seizures (r = 0.93, p = 0.001). The extent of perilesional FMZ PET abnormalities was independent of the seizure number and showed an excellent correspondence with spiking cortex, the resection of which resulted in seizure-free outcome in all but one operated patient. Remote FMZ PET abnormalities (n = 6) were associated with early age at seizure onset (p = 0.048) and appeared in ipsilateral synaptically connected regions from the lesion area. CONCLUSIONS: Three-dimensional surface-rendered FMZ PET is able to delineate perilesional epileptic cortex, and it may be especially useful to localize such areas in patients with extensive perilesional glucose hypometabolism associated with a large number of seizures. Remote FMZ PET abnormalities in patients with early onset and long duration of epilepsy might represent secondary epileptogenesis, but this requires further study.     

Glucose and [11C]flumazenil positron emission tomography abnormalities of thalamic nuclei in temporal lobe epilepsy

OBJECTIVES: To analyze interictal patterns of thalamic nuclei glucose metabolism and benzodiazepine receptor binding in patients with medically intractable temporal lobe epilepsy (TLE) using high-resolution 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and [11C]flumazenil (FMZ) PET. BACKGROUND: Structural and glucose metabolic abnormalities of the thalamus are considered important in the pathophysiology of TLE. The differential involvement of various thalamic nuclei in humans is not known. METHODS: Twelve patients with TLE underwent volumetric MRI, FDG and FMZ PET, and prolonged video-EEG monitoring. Normalized values and asymmetries of glucose metabolism and FMZ binding were obtained in three thalamic regions (dorsomedial nucleus [DMN], pulvinar, and lateral thalamus [LAT]) defined on MRI and copied to coregistered, partial-volume-corrected FDG and FMZ PET images. Hippocampal and amygdaloid FMZ binding asymmetries and thalamic volumes also were measured. RESULTS: The DMN showed significantly lower glucose metabolism and FMZ binding on the side of the epileptic focus. The LAT showed bilateral hypermetabolism and increased FMZ binding. There was a significant correlation between the FMZ binding asymmetries of the DMN and amygdala. The PET abnormalities were associated with a significant volume loss of the thalamus ipsilateral to the seizure focus. CONCLUSIONS: Decreased [11C]flumazenil (FMZ) binding and glucose metabolism of the dorsomedial nucleus (DMN) are common and have strong lateralization value for the seizure focus in human temporal lobe epilepsy. Decreased benzodiazepine receptor binding can be due to neuronal loss, as suggested by volume loss, but also may indicate impaired gamma-aminobutyric acid (GABA)ergic transmission in the DMN, which has strong reciprocal connections with other parts of the limbic system. Increased glucose metabolism and FMZ binding in the lateral thalamus could represent an upregulation of GABA-mediated inhibitory circuits.     

Positron emission tomography in presurgical localization of epileptic foci

The success of cortical resection for intractable epilepsy of neocortical origin is highly dependent on the accurate presurgical delineation of the regions responsible for generating seizures. In addition to EEG and structural imaging studies, functional neuroimaging such as positron emission tomography (PET) can assist lateralization and localization of epileptogenic cortical areas. In the presented studies, objectively delineated focal PET abnormalities have been analyzed in patients (mostly children) with intractable epilepsy, using two different tracers: 2-deoxy-2-[18F]fluoro-D-glucose (FDG), that measures regional brain glucose metabolism, and [11C]flumazenil (FMZ), that binds to GABAA receptors. The PET abnormalities were correlated with scalp and intracranial EEG findings, structural brain abnormalities, as well as surgical outcome data. In patients with extratemporal foci and no lesion on MRI, FMZ PET was more sensitive than FDG PET for identification of the seizure onset zone defined by intracranial EEG monitoring. In contrast, seizures commonly originated from the border of hypometabolic cortex detected by FDG PET suggesting that such areas are most likely epileptogenic, and should be addressed if subdural EEG is applied to delineate epileptic cortex. In patients with cortical lesions, perilesional cortex with decreased FMZ binding was significantly smaller than corresponding areas of glucose hypometabolism, and correlated well with spiking cortex. Extent of perilesional hypometabolism, on the other hand, showed a correlation with the life-time number of seizures suggesting a seizure-related progression of brain dysfunction. FMZ PET proved to be also very sensitive for detection of dual pathology (coexistence of an epileptogenic cortical lesion and hippocampal sclerosis). This has a major clinical importance since resection of both the cortical lesion and the atrophic hippocampus is required to achieve optimal surgical results. Finally, the author demonstrated that in patients with neocortical epilepsy, FDG PET abnormalities correctly regionalize the epileptogenic area, but their size is not related to the extent of epileptogenic tissue to be removed. In contrast, complete resection of cortex with decreased FMZ binding predicts good surgical outcome suggesting that application of FMZ PET can improve surgical results in selected patients with intractable epilepsy of neocortical origin.     

18F-FCWAY and 18F-FDG PET in MRI-negative temporal lobe epilepsy

Background: Positron emission tomography (PET) with ¹⁸F‐fluorodeoxyglucose (FDG) shows widespread hypometabolism even in temporal lobe epilepsy (TLE) patients with mesial temporal foci. ¹⁸F‐trans‐4‐fluoro‐N‐2‐[4‐(2‐methoxyphenyl) piperazin‐1‐yl]ethyl‐N‐(2‐pyridyl)cyclohexane carboxamide (¹⁸F‐FCWAY) PET may show more specific 5‐HT_1A‐receptor binding reduction in seizure initiation than in propagation regions. ¹⁸FCWAY PET might be valuable for detecting epileptic foci, and distinguishing mesial from lateral temporal foci in MRI‐negative patients with TLE. Methods: We performed ¹⁸F‐FCWAY‐PET and ¹⁸F‐FDG‐PET in 12 MRI‐negative TLE patients who had had either surgery or subdural electrode recording, and 15 healthy volunteers. After partial volume correction for brain atrophy, free fraction‐corrected volume of distribution (V/f1) measurement and asymmetry indices (AIs) were computed. We compared ¹⁸F‐FCWAY‐PET and ¹⁸F‐FDG‐PET results with scalp video electroencephalography (EEG), invasive EEG, and surgical outcome. Results: Mean ¹⁸F‐FCWAY V/f1, compared with normal controls, was decreased significantly in fusiform gyrus, hippocampus, and parahippocampus ipsilateral to epileptic foci, and AIs were significantly greater in hippocampus, parahippocampus, fusiform gyrus, amygdala, and inferior temporal regions. Eleven patients had clearly lateralized epileptogenic zones. Nine had congruent, and two nonlateralized, ¹⁸F‐FCWAY PET. One patient with bitemporal seizure onset had nonlateralized ¹⁸F‐FCWAY‐PET. ¹⁸F‐FDG‐PET showed congruent hypometabolism in 7 of 11 EEG‐lateralized patients, bilateral hypometabolic regions in one, contralateral hypometabolism in one, as well as lateralized hypometabolism in the patient with bitemporal subdural seizure onset. Patients with mesial temporal foci tended to have lower superior and midtemporal ¹⁸F‐FCWAY V/f1 binding AI than those with lateral or diffuse foci. Conclusion: ¹⁸F‐FCWAY‐PET can detect reduced binding in patients with normal MRI, and may be more accurate than ¹⁸F‐FDG‐PET.     

[11ClFlumazenil PET in Patients with Epilepsy with Dual Pathology

PURPOSE: Coexistence of hippocampal sclerosis and a potentially epileptogenic cortical lesion is referred to as dual pathology and can be responsible for poor surgical outcome in patients with medically intractable partial epilepsy. [11C]Flumazenil (FMZ) positron emission tomography (PET) is a sensitive method for visualizing epileptogenic foci. In this study of 12 patients with dual pathology, we addressed the sensitivity of FMZ PET to detect hippocampal abnormalities and compared magnetic resonance imaging (MRI) with visual as well as quantitative FMZ PET findings. METHODS: All patients underwent volumetric MRI, prolonged video-EEG monitoring, and glucose metabolism PET before the FMZ PET. MRI-coregistered partial volume-corrected PET images were used to measure FMZ-binding asymmetries by using asymmetry indices (AIs) in the whole hippocampus and in three (anterior, middle, and posterior) hippocampal subregions. Cortical sites of decreased FMZ binding also were evaluated by using AIs for regions with MRI-verified cortical lesions as well as for non-lesional areas with visually detected asymmetry. RESULTS: Abnormally decreased FMZ binding could be detected by quantitative analysis in the atrophic hippocampus of all 12 patients, including three patients with discordant or inconclusive EEG findings. Decreased FMZ binding was restricted to only one subregion of the hippocampus in three patients. Areas of decreased cortical FMZ binding were obvious visually in all patients. Decreased FMZ binding was detected visually in nonlesional cortical areas in four patients. The AIs for these nonlesional regions with visual asymmetry were significantly lower than those for regions showing MRI lesions (paired t test, p = 0.0075). CONCLUSIONS: Visual as well as quantitative analyses of FMZ-binding asymmetry are sensitive methods to detect decreased benzodiazepine-receptor binding in the hippocampus and neocortex of patients with dual pathology. MRI-defined hippocampal atrophy is always associated with decreased FMZ binding, although the latter may be localized to only one sub-region within the hippocampus. FMZ PET abnormalities can occur in areas with normal appearance on MRI, but FMZ-binding asymmetry of these regions is lower when compared with that of lesional areas. FMZ PET can be especially helpful when MRI and EEG findings of patients with intractable epilepsy are discordant.     

Focal decreases of cortical GABAA receptor binding remote from the primary seizure focus: What do they indicate?

Purpose: To determine the electroclinical significance and histopathological correlates of cortical γ‐aminobutyric acid_A(GABA_A) receptor abnormalities detected in and remote from human neocortical epileptic foci. Methods: Cortical areas with decreased¹¹C‐flumazenil (FMZ) binding were objectively identified on positron emission tomography (PET) images and correlated to intracranial electroencephalography (EEG) findings, clinical seizure variables, histology findings, and surgical outcome in 20 patients (mean age, 9.9 years) with intractable partial epilepsy of neocortical origin and nonlocalizing magnetic resonance imaging (MRI). Results: Focal decrease of cortical FMZ binding was detected in the lobe of seizure onset in 17 (85%) patients. Eleven patients (55%) had 17 remote cortical areas with decreased FMZ binding outside the lobe of seizure onset. Thirteen of those 16 (81%) of the 17 remote cortical regions that were covered by subdural EEG were around cortex showing rapid seizure spread on intracranial EEG. Remote FMZ PET abnormalities were associated with high seizure frequency and, when resected, showed gliosis in all six cases where material was available. Higher number of unresected cortical regions with decreased FMZ binding was associated with poorer surgical outcome. Conclusions: Focal decreases of cortical GABA_A receptor binding on PET may include cortical regions remote from the primary focus, particularly in patients with high seizure frequency, and these regions are commonly involved in rapid seizure propagation. Although these regions may not always need to be resected to achieve seizure freedom, a careful evaluation of cortex with decreased GABA_A receptor binding prior to resection using intracranial EEG may facilitate optimal surgical outcome in patients with intractable neocortical epilepsy.     

Functional neuroimaging in the preoperative evaluation of children with drug-resistant epilepsy

Functional neuroimaging Although the primary imaging modality in the management of epilepsy is magnetic resonance imaging MRI, functional neuroimaging with positron-emission tomography (PET) and single photon emission computed tomography (SPECT) often provides complementary information and, in a number of situations, provides unique information that cannot be obtained with MRI. The most commonly used PET tracers used for epilepsy evaluation are 2-deoxy-2-[¹⁸F]fluoro-d-glucose (FDG) and [¹¹C]flumazenil (FMZ). Recently, interictal PET with alpha-[¹¹C]methyl-l-tryptophan was found to be highly specific for the epileptic focus and can differentiate between epileptogenic and nonepileptogenic lesions in the same patient (e.g., in patients with tuberous sclerosis).Discussion In this review, we discuss clinical applications of these three PET tracers in drug-resistant temporal and extratemporal lobe epilepsy, selected epilepsy syndromes of childhood, lesional and nonlesional epilepsy, and the challenges of imaging secondary epileptic foci. A brief discussion of SPECT applications in epilepsy is also included. With further development of new tracers highly sensitive and specific for epileptogenic brain regions, the presurgical evaluation of refractory epilepsy will be greatly facilitated. Approximately 0.5 to 1.0% of the population suffer from epilepsy, of which 15–20% are intractable. Infants and children, whose seizures have a focal onset are refractory to anticonvulsants and are prolonged, tend to have the worst cognitive outcome [Meador KJ, Neurology 58 (Suppl 5):S21–S26, 2002]. Seizures themselves affect the developing brain and contribute to an adverse neurologic outcome (Holmes, Pediatric Neurology 33:1–110, 2005).Conclusion Therefore, in treating children with intractable epilepsy, it is important to consider seizure control and to give allowance for normal cognitive development.     

发作间期颞叶癫痫的18F-FDG PET 显像研究

目的：采用诊断试验评价方法评估发作间期^18F-FDG PET显像对颞叶癫痫定性和病业定位的诊断价值，探讨其外科治疗的意义。方法：26例CT或MRI检查正常，经临床及脑电图诊断的颞叶癫痫患者在同期进行发作间期^18F-FDG PET脑显像，图像通过目测和半定量的方法进行分析，PET显示的低代谢区行皮层脑电图（EcoG）或深部脑电图（DEEG）描记以评估^18F-FDG PET检测癫痫灶的特异性，17例定位明确的单侧颞叶癫痫行前颞叶切除术，术手进行随访。2例PET未检出癫痫灶，7例DEEG定位双侧病灶未行手术治疗。结果：26例颞叶癫痫中，发现^18F-FDG PET对癫痫灶检出的灵敏度为92%（24/26），特异度为87%(21/24)。结论：从颞叶癫痫的定性定位诊断来看，发作间期^18F-FDG PET脑显像对癫痫灶的检出率较高，但^18F-FDG PET显示的低代谢区与癫痫灶的位置并非完全重叠，尚需要其他的诊断措施加以肯定，^18F-FDG PET和皮层脑电图或深部脑电图对癫痫病灶定位的一致性是手术成功的关键。     

Localizing value of alpha-methyl-L-tryptophan PET in intractable epilepsy of neocortical origin.

BACKGROUND: [(11)C] alpha-methyl-L-tryptophan (alpha-MTrp) has been developed as a tracer for the study of the synthesis of serotonin in the brain with PET. However, it has been shown that in pathologic conditions the tracer may reflect the activation of kynurenine metabolism. Increased levels of serotonin and quinolinic acid have been described in resected epileptogenic cortex, raising the possibility that alpha-MTrp can localize seizure foci in patients with intractable partial epilepsy. The authors assessed the uptake of alpha-MTrp in 18 patients (11 men, mean +/- SD age 27.1 +/- 10.1 years, range 13 to 54) with intractable partial epilepsy to correlate the PET findings with the epileptogenic area defined by electroclinical and neuroimaging data. METHOD: Seven patients with cortical dysplasia (CD) and 11 with partial epilepsy in which conventional MRI and fluorine-18-deoxyglucose ((18)FDG)-PET studies failed to detect any abnormality were studied. All underwent scalp EEG monitoring during the PET scan to exclude ictal events and estimate the interictal epileptic activity. RESULTS: In seven patients (39%; CD four and cryptogenic partial epilepsy three), PET showed focal increased uptake of alpha-MTrp corresponding to the epileptogenic area. alpha-MTrp uptake in the epileptic focus correlated with the frequency of interictal spikes (r = 0.7, p < 0.05). CONCLUSIONS: alpha-MTrp-PET may be of value in the localization of the epileptogenic area not only in patients with visible dysplastic lesions, but also in those with cryptogenic partial epilepsy.     

Prognostic factors in anterior temporal lobe resections for mesial temporal lobe epilepsy: multivariate analysis

PURPOSE: Even though there have been several studies on the prognostic factors of temporal lobe epilepsy (TLE) after lobectomy, no studies have been performed for homogeneous mesial TLE. Furthermore, most studies on the predictors of outcome of epileptic surgery were based on univariate analyses and did not consider modern epileptic surgery investigation modalities such as brain magnetic resonance imaging (MRI) and positron emission tomography (PET). We attempted to identify the prognostic factors in anterior temporal lobectomy (ATL) for mesial TLE with multivariate analysis. METHODS: Ninety-three patients with mesial TLE (54 men and 39 women, mean age at surgery, 28.3 +/- 8.2 years) were included in the study. The primary outcome variable was the status of patients in the second postoperative year, classified as either seizure free (except aura), or not seizure free. Clinical, electroencephalographic, MRI, PET, Wada test, and pathological data were considered. RESULTS: Seventy-eight (84.0%) patients had remission of seizures. With univariate analysis, age at surgery (p < 0.001), epilepsy duration before surgery (p = 0.04), and ipsilateral hippocampal sclerosis on MRI (p = 0.02) were found to be significant. By using multivariate analysis, age at surgery (p = 0.001) and ipsilateral hippocampal sclerosis on MRI (p = 0.03) were found to be the most significant prognostic factors. CONCLUSIONS: Age at surgery and hippocampal sclerosis are independent prognostic factors for ATL in mesial TLE. These findings suggest that mesial TLE may be a progressive disorder, and surgical outcome is better when early ATL is performed.     

Multimodality imaging for improved detection of epileptogenic foci in tuberous sclerosis complex

OBJECTIVE: Using interictal alpha-[11C]methyl-l-tryptophan ([11C]AMT) PET scan, the authors have undertaken a quantitative analysis of all tubers visible on MRI or 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) PET, to determine the relationship between [11C]AMT uptake and epileptic activity on EEG. BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder, often associated with cortical tubers and intractable epilepsy. The authors have shown previously that [11C]AMT PET scans show high tracer uptake in some epileptogenic tubers and low uptake in the remaining tubers. METHODS: Eighteen children, age 7 months to 16 years, were studied. Patients underwent video-EEG monitoring, PET scans of [11C]AMT and [18F]FDG, and T2-weighted or fluid-attenuated inversion recovery (FLAIR) MRI. [11C]AMT uptake values were measured in 258 cortical tubers delineated with coregistered MRI or [18F]FDG scans. Uptake ratios were calculated between the [11C]AMT uptake in tubers and those for normal cortex (tuber/normal cortex). Using the region of epileptiform activity, the authors performed receiver operator characteristics (ROC) analysis and determined the optimal uptake ratio for detecting presumed epileptogenic tubers. RESULTS: Tuber uptake ratios ranged from 0.6 to 2.0. Tuber uptake ratios in the epileptic lobes were higher than those in the nonepileptic lobes (p < 0.0001). All 15 patients with focal seizure activity showed one or more lesions with uptake ratio above 0.98 in the epileptic lobe. ROC analysis showed that a tuber uptake ratio of 0.98 resulted in a specificity of 0.91. CONCLUSIONS: Cortical tubers with [11C]AMT uptake greater than or equal to normal cortex are significantly related to epileptiform activity in that lobe. Together, interictal [11C]AMT PET and FLAIR MRI improve the detection of potentially epileptogenic tubers in patients with TSC being evaluated for epilepsy surgery.     

Contralateral temporal hypometabolism on positron emission tomography in temporal lobe epilepsy

Introduction — No detailed case studies report lateralised hypometabolism on positron emission tomography (PET) contralateral to the epileptogenic focus in temporal lobe epilepsy (TLE). Material and methods — We performed ¹⁸F fluorodeoxyglucose (FDG) PET in two intractable TLE patients. Results — One had right temporal interictal spikes on electroencephalography (EEG) and a right medial temporal lobe lesion on magnetic resonance imaging (MRI). FDG-PET showed decreased uptake in the left temporal lobe. Right temporal ictal onset, with bilateral interictal epileptiform activity, occurred on intracranial EEG. He is seizure free after right temporal lobectomy and ganglioglioma resection. The second had right temporal lobe interictal and ictal EEG activity. MRI demonstrated right anteriomedial temporal increased T2 signal. Neuropsychology revealed bilateral cognitive dysfunction. FDG-PET showed left anterior temporal and lateral frontal hypometabolism. He is seizure free after right temporal lobectomy. Conclusion — These findings suggest that regional uptake asymmetry on FDG-PET may be give misleading lateralising information in TLE.     

颞叶癫 的EEG和MR术前定位研究

目的：探讨 ＥＥＧ、ＭＲ对颞叶癫癎（ＴＬＥ）术前定位。方法：用 ＭＲ、ＥＥＧ对 ２０例 ＴＬＥ病例进行术前定位,与术中 ＥＥＧ和术后随访结果比较。结果：２０例病例中１７例依据ＭＲ及ＥＥＧ获得定位,主要在海马区域病变１２例,前颞叶５例．另３例ＭＲ检查正常,依据多次ＥＥＧ检查获得定位,随访疗效满意。结论：ＥＥＧ是诊断ＴＬＥ的重要手段,ＭＲ可对继发性ＴＬＥ作出正确诊断,ＭＲ对海马硬化检查可协助ＥＥＧ对ＴＬＥ定位诊断。     

11C-flumazenil PET in patients with refractory temporal lobe epilepsy and normal MRI

BACKGROUND: Using 11C-flumazenil (FMZ) PET with correction for partial-volume effect, reductions of central benzodiazepine receptor (cBZR) binding can be detected reliably in vivo on remaining neurons in sclerotic hippocampi of patients with mesial temporal lobe epilepsy (TLE). OBJECTIVE: To delineate abnormalities of 11C-FMZ binding in patients with medically refractory TLE and normal quantitative MRI. METHODS: Analysis of parametric images of FMZ volume of distribution (Vd) using two complementary approaches: 1) MRI-based volume of interest (VOI) approach with partial volume effect correction for multiple hippocampal and extrahippocampal VOIs; and 2) statistical parametric mapping (SPM) to localize significant 11C-FMZ binding changes objectively on a voxel-by-voxel basis. RESULTS: Significant abnormalities of absolute FMZ-Vd were found after partial volume effect correction in 5 of 10 patients: unilateral decrease in the amygdala ipsilateral to the EEG focus (1), unilateral hippocampal decreases and bilateral temporal and extratemporal neocortical decreases (2), unilateral increase in the temporal neocortex together with extratemporal neocortical increases (1), and bilateral posterior hippocampal increases together with temporal neocortical increases (1). In the three patients with extratemporal neocortical changes, the concomitant unilateral hippocampal or temporal neocortical changes were contralateral to the presumed epileptic focus. Significant asymmetries of FMZ-Vd between homologous regions were found in six patients. In four of those patients, absolute FMZ-Vd for the homologous regions were within normal limits, with two of the four patients showing relatively higher hippocampal values ipsilateral to the presumed epileptic focus. SPM analysis localized significant abnormalities of FMZ-Vd in similar locations in three of the seven patients in whom VOI analysis detected significant changes. In addition, SPM indicated significant unilateral contralateral hippocampal decreases in an eighth patient. However, both methods failed to localize epileptic foci in two patients identified by depth-EEG recordings. CONCLUSIONS: 11C-FMZ PET showed focal increases as well as decreases of FMZ binding in 80% of patients with refractory TLE and normal high-quality MRI but was not consistently helpful in localizing the epileptic foci.     

Surgical treatment of West syndrome.

The discovery of focal or multifocal cortical lesions using magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning in the majority of infants with West syndrome has led to a surgical approach in the treatment of some patients with intractable infantile spasms. The locations of these lesions should be concordant with localization of focal ictal and/or interictal electroencephalographic (EEG) abnormalities prior to proceeding with cortical resection. When a single lesion is present on the MRI or PET, and there is good correlation with EEG localization, surgical treatment is generally quite favorable in terms of both seizure control and cognitive development. Interictal glucose metabolism PET scans in children with intractable cryptogenic infantile spasms show unifocal cortical hypometabolism in about 20% of cases. In the majority, however, multifocal asymmetric hypometabolism is suggestive of multifocal underlying lesions, possibly multifocal cortical dysplasia. When the pattern of glucose hypometabolism is symmetric, a lesional etiology is less likely, thus neurometabolic or neurogenetic disorders should be considered. Therefore, the pattern of glucose hypometabolism on PET in infants with intractable cryptogenic spasms is a useful guide to decide whether a medical or surgical approach should be undertaken. In order to achieve the best cognitive outcome with surgery, it is important to resect the entire 'nociferous' area rather than just the seizure focus. Our research with new PET imaging probes has attempted to provide a comprehensive evaluation of the epileptogenic zone including the 'nociferous' cortex. We have used [(11)C]flumazenil (FMZ), which labels gamma aminobutyric acid(A) (GABA(A)) receptors, and have found this to be particularly useful in showing: (i) decreased receptor binding with medial temporal involvement thus indicating resection of medial temporal structures, (ii) the peri-lesional epileptogenic zone surrounding MRI lesions, (iii) the seizure onset zone in MRI-negative cases, and (iv) potential secondary epileptic foci. Another recently developed PET probe, alpha[(11)C]methyl-L-tryptophan (AMT) which is a precursor for the serotonin and the kynurenine metabolism pathways, is capable of differentiating between epileptogenic and non-epileptogenic tubers in patients with tuberous sclerosis complex and intractable epilepsy (including infantile spasms). Subsequently, we have applied AMT PET in patients with multifocal cortical dysplasia to determine the predominant seizure focus, and the results have been promising with regard to seizure control but not cognitive development. Thus, the introduction of newer more specific PET probes for epilepsy has led to improved and more accurate localization of seizure foci that should ultimately improve outcome of epilepsy surgery in West syndrome.     

MRI与PET在颞叶癫癎中定位价值的比较

目的 比较ＭＲＩ及ＦＤＧ－ＰＥＴ在颞叶癫癎致癎灶定位中的价值,探讨癫癎外科术前定位的方法以及手术预后的判断。方法 以手术后癫癎控制状况为标准,对３０例颞叶癫癎患者的术前ＭＲＩ和ＦＤＧ－ＰＥＴ的结果进行比较,分析ＭＲＩ及ＰＥＴ各自在癫癎致癎灶定位中的价值。结果ＭＲＩ有良好的脑结构分辨能力,对于症状性癫癎的定位价值高,当ＭＲＩ显示海马硬化时,对致癎灶定位的意义大,术后癫癎发作完全控制的可能性大。发作间期ＰＥＴ对于颞叶癫癎定位的敏感性高于ＭＲＩ,但ＰＥＴ低代谢的范围往往超过致癎灶。与ＰＥＴ的目测方法比较,ＰＥＴ半定量分析并不能提高致癎灶定位的准确性及对手术效果的预测。结论　ＭＲＩ与ＰＥＴ检查结合可以提高致癎灶定位的准确性及对手术效果的预测,减少颅内记录的应用。     

Metabolic changes of subcortical structures in intractable focal epilepsy

PURPOSE: Intractable focal epilepsy is commonly associated with cortical glucose hypometabolism on interictal 2-deoxy-2[18F]-fluoro-D-glucose (FDG) positron emission tomography (PET). However, subcortical brain structures also may show hypometabolism on PET and volume changes on magnetic resonance imaging (MRI) studies, and these are less well understood in terms of their pathophysiology and clinical significance. In the present study, we analyzed alterations of glucose metabolism in subcortical nuclei and hippocampus by using FDG-PET in young patients with intractable epilepsy. METHODS: Thirty-seven patients (mean age, 7.5 years; age range, 1-27 years) with intractable frontal (n = 23) and temporal (n = 14) lobe epilepsy underwent FDG-PET scanning as part of their presurgical evaluation. Normalized glucose metabolism was measured in the thalamus and caudate and lentiform nuclei, as well as in hippocampus, both ipsi- and contralateral to the epileptic focus, and correlated with duration and age at onset of epilepsy, presence or absence of secondary generalization, location of the epileptic focus, and extent of cortical glucose hypometabolism. RESULTS: Long duration of epilepsy was associated with lower glucose metabolism in the ipsilateral thalamus and hippocampus. Duration of epilepsy was a significant predictor of ipsilateral thalamic glucose metabolism in both temporal and frontal lobe epilepsy. Presence of secondarily generalized seizures also was associated with lower normalized metabolism in the ipsilateral thalamus and hippocampus. Extent of cortical hypometabolism did not correlate with subcortical metabolism, and glucose metabolism in the caudate and lentiform nuclei did not show any correlation with the clinical variables. CONCLUSIONS: The findings suggest that metabolic dysfunction of the thalamus ipsilateral to the seizure focus may become more severe with long-standing temporal and frontal lobe epilepsy, and also with secondary generalization of seizures.     

Low incidence of abnormal (18)FDG-PET in children with new-onset partial epilepsy: a prospective study

OBJECTIVE: Patients with refractory partial epilepsy often exhibit regional hypometabolism. It is unknown whether the metabolic abnormalities are present at seizure onset or develop over time. METHODS: The authors studied 40 children within 1 year of their third unprovoked partial seizure with EEG, MRI, and [(18)F]-fluorodeoxyglucose ((18)FDG)-PET (mean age at seizure onset = 5.8 years, range 0.9 to 11.9 years; mean epilepsy duration = 1.1 years, range 0.3 to 2.3 years; mean number of seizures = 30, range 3 to 200). The authors excluded children with abnormal structural MRI, except four with mesial temporal sclerosis and two with subtle hippocampal dysgenesis. (18)FDG-PET was analyzed with a region of interest template. An absolute asymmetry index, [AI], greater than 0.15 was considered abnormal. RESULTS: Thirty-three children had a presumptive temporal lobe focus, five frontotemporal, and two frontal. Mean AI for all regions was not different from 10 normal young adults, even when children less likely to have a temporal focus were excluded. Eight of 40 children (20%) had focal hypometabolism, all restricted to the temporal lobe, especially inferior mesial and inferior lateral regions. Abnormalities were ipsilateral to the presumed temporal lobe ictal focus. CONCLUSIONS: Abnormalities of glucose utilization may be less common and profound in children with new-onset partial seizures than in adults with chronic partial epilepsy. Although these patients' prognosis is uncertain, resolution of epilepsy after three documented seizures is uncommon. If the subjects develop a higher incidence of hypometabolism in the future with planned follow-up studies, metabolic dysfunction may be related to persistent epilepsy rather than present at seizure onset.