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.     

Is epileptogenic cortex truly hypometabolic on interictal positron emission tomography?

Positron emission tomography (PET) of glucose metabolism is often applied for the localization of epileptogenic brain regions, but hypometabolic areas are often larger than or can miss epileptogenic cortex in nonlesional neocortical epilepsy. The present study is a three-dimensional brain surface analysis designed to demonstrate the functional relation between glucose PET abnormalities and epileptogenic cortical regions. Twelve young patients (mean age, 10.8 years) with intractable epilepsy of neocortical origin underwent chronic intracranial electroencephalographic monitoring. The exact location of the subdural electrodes was determined on high-resolution three-dimensional reconstructed magnetic resonance imaging scan volumes. The electrodes were classified according to their locations over cortical areas, which were defined as hypometabolic, normometabolic, or at the border between hypometabolic and normal cortex (metabolic "border zones") based on interictal glucose PET. Electrodes with seizure onset were located over metabolic border zones significantly more frequently than over hypometabolic or normometabolic regions. Seizure spread electrodes also more frequently overlay metabolic border zones than hypometabolic regions. These findings suggest that cortical areas with hypometabolism should be interpreted as regions mostly not involved in seizure activity, although epileptic activity commonly occurs in the surrounding cortex. This feature of hypometabolic cortex is remarkably similar to that of structural brain lesions surrounded by epileptogenic cortex. Cortical areas bordering hypometabolic regions can be highly epileptogenic and should be carefully assessed in presurgical evaluations.     

Positron emission tomography studies of cerebral glucose metabolism in chronic partial epilepsy

Positron emission tomography (PET) performed with [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG) was used to measure local cerebral metabolic rate for glucose (lCMRGlc) interictally in 31 patients with chronic partial epilepsy and 16 age-matched normal subjects. Hypometabolic zones were visualized in 25 patients (81%). Cortical lCMRGlc in hypometabolic zones was within 2 standard deviations of the mean for normal temporal cortex in all but 8 patients. However, in 24 patients asymmetry between the hypometabolic cortex and homologous contralateral cortex was more than 2 standard deviations above the mean cortical asymmetry for normals. There was good correlation between hypometabolic zones and electroencephalogram (EEG) foci in patients with unilateral well-defined EEG foci. Diffuse or shifting EEG abnormalities were often associated with normal PET scans. Of 28 patients who underwent magnetic resonance imaging, 10 showed focal temporal lobe abnormalities corresponding to focal hypometabolism. While the [18F]FDG PET scan cannot currently localize an epileptogenic zone independently, the absence of focal hypometabolism or its presence contralateral to a presumed EEG focus suggests the need for additional electrophysiological data.     

Positron emission tomography in epilepsy: correlative study

Positron emission tomography (PET) was performed with the 18F-fluoro-deoxy-glucose method on 29 patients with epilepsy (generalized epilepsy, 4; partial epilepsy, 24; undetermined type, 1). The subjects were restricted to patients with epilepsy without focal abnormality on X-CT. All the patients with generalized epilepsy showed a normal pattern on PET. Fourteen out of the 24 patients with partial epilepsy and the 1 with epilepsy of undetermined type showed focal hypometabolism on PET. The hypometabolic zone was localized in areas including the temporal cortex in 11 patients, frontal in 2 and thalamus in 1. The location of hypometabolic zone and that of interictal paroxysmal activity on EEG were well correlated in most patients. The patients with poorly-controlled seizure showed a higher incidence of PET abnormality (12 out of 13) than those with well-controlled seizures (2 out of 11). The incidence of abnormality on PET and MRI and the location of both abnormality were not necessarily coincident. These results indicated that the PET examination in epilepsy provides valuable information about the location of epileptic focus, and that the findings on PET in patients with partial epilepsy may be one of the good indicators about the intractability of partial epilepsy, and that PET and MRI provide complementary information in the diagnosis of epilepsy.     

Sturge-Weber syndrome: correlation between clinical course and FDG PET findings

OBJECTIVE: To determine whether the extent and degree of glucose hypometabolism defined by PET correlate with seizure characteristics, cognitive function, and interictal EEG abnormalities in children with unilateral cerebral involvement of Sturge-Weber syndrome (SWS). METHODS: 2-Deoxy-2[18F]fluoro-D-glucose (FDG) PET was performed in 13 children (age range 0.7 to 15.1 years; five boys, eight girls) with unilateral SWS. Based on asymmetries between homologous cortical areas in FDG PET images, cortical areas of mildly (10% to 20% decrease), and severely (>20% decrease) asymmetric cortical metabolism were defined. These areas were normalized to the size of the ipsilateral hemisphere and correlated with clinical seizure characteristics, full-scale IQ, and interictal EEG abnormalities. RESULTS: Both seizure frequency (p = 0.027) and lifetime number of seizures (p = 0.017) showed a positive correlation with the area (expressed as the percentage of cortical area of ipsilateral hemisphere) of mildly asymmetric cortical metabolism. Patients with higher IQ had a shorter duration of epilepsy (p = 0.044) and a larger area of severely asymmetric cortical metabolism (p = 0.044). Patients with bilateral interictal EEG abnormalities had larger lifetime number of seizures (p = 0.042), lower IQ (p = 0.024), and smaller area of severely asymmetric cortical metabolism (p = 0.019) than those with only ipsilateral EEG abnormalities. CONCLUSIONS: Association of severely asymmetric cortical metabolism with relatively preserved cognitive function in SWS suggests that functional reorganization occurs more readily when cortex is severely rather than mildly damaged. Therefore, the area of mildly asymmetric cortical metabolism may exert a nociferous effect on the remaining of the brain. Thus, the extent and degree of glucose asymmetry detected by PET are sensitive markers of seizure severity and cognitive decline in SWS.     

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.     

The prognostic value of [F]FDG-PET in nonrefractory partial epilepsy

PURPOSE: Regional abnormalities of cerebral glucose metabolism, as identified by 18-fluorodeoxyglucose positron emission tomography (FDG-PET) have prognostic value regarding the outcome of epilepsy surgery in patients with refractory partial epilepsy. The value of FDG-PET abnormalities in nonrefractory patients has not been investigated systematically. This study examines whether FDG-PET could be used for early identification of nonrefractory epilepsy in patients who will become pharmacoresistant later during the course of their disease. METHODS: We investigated interictal abnormalities of cerebral glucose metabolism by using FDG-PET in 125 consecutive patients with nonrefractory cryptogenic partial epilepsy and normal cranial magnetic resonance imaging (MRI), and we compared relative changes in seizure frequency in 90 patients after > or =2 years of follow-up. RESULTS: Regional asymmetry of tracer distribution was seen in 43 of the 90 patients. Forty-one patients had regional glucose hypometabolism in the temporal and two patients in an extratemporal region. No difference between patients with and without a hypometabolic focus was found regarding seizure freedom after follow-up. This held true also for the subgroup of patients with epilepsy onset within 1 year before admission. Only patients with regional glucose metabolism showed an increase in seizure frequency. Multivariate analysis showed that only anticonvulsive treatment before index admission and the possibility of localizing the epileptogenic focus by using all available clinical and EEG data were independently associated with continuing seizures after a median follow-up period of 43 months. CONCLUSIONS: Regional hypometabolism in FDG-PET is not significantly associated with a lower likelihood of successful anticonvulsant drug therapy in patients with nonrefractory partial epilepsy. Careful analysis of all routinely available clinical and neurophysiologic data has a much better predictive power to identify patients with medically refractory epilepsy early in the course of the disease. However, if PET data are available, they could help in identifying patients with a less benign course.     

Transient focal cortical increase of interictal glucose metabolism in Sturge-Weber syndrome: implications for epileptogenesis

Purpose: To investigate clinical correlates and longitudinal course of interictal focal cortical glucose hypermetabolism in children with Sturge‐Weber syndrome (SWS). Methods: Fluorodeoxyglucose positron emission tomography (FDG‐PET) scans of 60 children (age range 3 months to 15.2 years) with Sturge‐Weber syndrome and epilepsy were assessed prospectively and serially for focal hypo‐ or hypermetabolism. Thirty‐two patients had two or more consecutive PET scans. Age, seizure variables, and the occurrence of epilepsy surgery were compared between patients with and without focal hypermetabolism. The severity of focal hypermetabolism was also assessed and correlated with seizure variables. Key Findings: Interictal cortical glucose hypermetabolism, ipsilateral to the angioma, was seen in nine patients, with the most common location in the frontal lobe. Age was lower in patients with hypermetabolism than in those without (p = 0.022). In addition, time difference between the onset of first seizure and the first PET scan was much shorter in children with increased glucose metabolism than in those without (mean: 1.0 vs. 3.6 years; p = 0.019). Increased metabolism was transient and switched to hypometabolism in all five children where follow‐up scans were available. Focal glucose hypermetabolism occurred in 28% of children younger than the age of 2 years. Children with transient hypermetabolism had a higher rate of subsequent epilepsy surgery as compared to those without hypermetabolism (p = 0.039). Significance: Interictal glucose hypermetabolism in young children with SWS is most often seen within a short time before or after the onset of first clinical seizures, that is, the presumed period of epileptogenesis. Increased glucose metabolism detected by PET predicts future demise of the affected cortex based on a progressive loss of metabolism and may be an imaging marker of the most malignant cases of intractable epilepsy requiring surgery in SWS.     

Identification of Frontal Lobe Epileptic Foci in Children Using Positron Emission Tomography

Summary: Purpose: Presurgical evaluation for intractable frontal lobe epilepsy (FLE) is difficult and invasive, partly because anatomic neuroimaging studies with computed tomography (CT) and magnetic resonance imaging (MRI) typically do not show a discrete lesion. In adult patients with FLE, functional neuroimaging of glucose metabolism with positron emission tomography (PET) is less sensitive in detecting focal metabolic abnormalities than in temporal lobe epilepsy (TLE). Comparable data on children with FLE are not available. Methods: We used high-resolution PET scanning of glucose metabolism to evaluate 13 children (age 17 months to 17 years; mean age 9.5 years) with intractable FLE being considered for surgical treatment. Only children with normal CT and MRI scans were included. Results: Hypometabolism including the frontal lobe was evident in 12 of the 13 children, was unilateral in 11 of 13, and was restricted to the frontal lobe in 8 of 13. One child showed bilateral frontal cortex hypometabolism and another had anictal PET scan demonstrating unilateral frontal cortex hyper-metabolism surrounded by hypometabolism. Additional hypo–metabolic areas outside the frontal cortex were observed in 5 children in parietal and/or temporal cortex. Localization of seizure onset on scalp EEG was available in 10 children and corresponded to the location of frontal lobe PET abnormality in 8. However, in 4 of the 10 children, the extent of hypometabolism exceeded the epileptogenic region indicated by ictal EEG. In 2 of the 13 children, the abnormality evident on EEG was more extensive than that evident on PET. In the remaining 3 children for whom only interictal EEG data were available, the PET foci did not correspond in location to the interictal EEG abnormalities. In 11 of the 13 children, the presumed region of seizure onset in the frontal lobe, as based on analysis of seizure semiology, corresponded to the locations of frontal lobe glucose metabolism abnormalities. Conclusions: Although high-resolution PET appears to be very sensitive in localizing frontal lobe glucose metabolic abnormalities in children with intractable FLE and normal CT/ MRI scans, the significance of extrafrontal metabolic disturbances requires further study; these may represent additional epileptogenic areas, effects of diaschisis, seizure propagation sites, or secondary epileptogenic foci.     

Bilateral medial prefrontal and temporal neocortical hypometabolism in children with epilepsy and aggression

PURPOSE: To identify brain regions with abnormal function in children with intractable partial epilepsy and aggressive behavior by using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET). METHODS: Six children (mean age, 9.9 years) with intractable partial epilepsy and aggressive behavior underwent detailed psychodevelopmental assessment and FDG-PET scanning. The objective technique of statistical parametric mapping (SPM) was applied to define focal abnormalities of glucose metabolism, and compared those with those of a group of normal adult subjects (n = 17) as well as age-matched children with epilepsy with similar seizure characteristics but without aggression (n = 7). The findings were analyzed further by using a region-of-interest (ROI) approach. RESULTS: The aggressive children all showed developmental delay, and four of them also manifested autistic symptoms. SPM analysis demonstrated extensive glucose hypometabolism in the aggressive group bilaterally in the temporal and prefrontal cortex compared with that in normal adult controls. A focal area of medial prefrontal glucose hypometabolism was defined in the aggressive children as compared with the nonaggressive pediatric group with SPM, whereas ROI comparison of these groups confirmed prefrontal hypometabolism and also showed glucose hypometabolism of the temporal neocortex in the aggressive children. Severity of aggression correlated inversely with glucose metabolism of the left temporal as well as bilateral medial prefrontal cortex. CONCLUSIONS: Bilateral prefrontal and temporal neocortical brain glucose hypometabolism in children with epilepsy and aggressive behavior may indicate a widespread dysfunction of cortical regions, which normally exert an inhibitory effect on subcortical aggressive impulses. PET studies may be used to elucidate the neurobiologic basis of aggressive behavior in children.     

The Use and Impact of Positron Computed Tomography Scanning in Epilepsy

Summary: Through the effective combination of instrumentation, tracer kinetic principles, and radiopharmaceuticals, positron computed tomography (PET) allows for the analytic, noninvasive measurement of local tissue physiology in humans. A large number of studies have already been performed in patients with epilepsy using ¹⁸F-fluorodeoxyglucose (FDG) to measure local cerebral glucose utilization. In patients with complex partial epilepsy who are candidates for surgery, hypometabolic zones have been seen consistently (70%) in the interictal state. These areas of hypometabolism have been related to electroencephalographic findings, surgical pathology, and clinical symptomatology. The complex anatomical and pathophysiological investigation of these hypometabolic zones is discussed. Ictal studies of patients with partial seizures have demonstrated a much more variable metabolic pattern which usually consists of hypermetabolism relative to baseline or interictal studies. Generalized epilepsy produced by electroconvulsive shock and petit mal epilepsy have been studied using FDG to estimate glucose metabolism. These studies demonstrated hypermetabolism in the ictal state, relative to interictal or postictal scans, but with a more generalized pattern than ictal studies of partial seizures. Methodological problems in the study of epilepsy with PET are discussed in detail. The investigation of interictal hypometabolism through animal models of epilepsy and quantitative autoradiography is described as a means to understand the human PET results. The impact and future direction of PET studies in epileptic populations will probably employ the use of behavioral, pharmacological, and electrophysiological maneuvers to provide more specific details about the fundamental pathophysiological mechanisms of specific aspects of epilepsy. These techniques may allow for a truly pathophysiological classification system for the common and unusual types of epilepsy, and through this classification system improve the therapeutic and prognostic clinical approach to patients     

Positron Emission Tomography in Epilepsy: Correlative Study

Abstract: Positron emission tomography (PET) was performed with the ¹⁸F-fluoro-deoxy-glucose method on 29 patients with epilepsy (generalized epilepsy, 4; partial epilepsy, 24; undetermined type, 1). The subjects were restricted to patients with epilepsy without focal abnormality on X-CT. All the patients with generalized epilepsy showed a normal pattern on PET. Fourteen out of the 24 patients with partial epilepsy and the 1 with epilepsy of undetermined type showed focal hypometabolism on PET. The hypomeiabolic zone was localized in areas including the temporal cortex in 11 patients, frontal in 2 and thalamus in 1. The location of hypometabolic zone and that of interictal paroxysmal activity on EEG were well correlated in most patients. The patients with poorly controlled seizure showed a higher incidence of PET abnormality (12 out of 13) than those with well-controlled seizures (2 out of 11). The incidence of abnormality on PET and MRI and the location of both abnormalities were not necessarily coincident. These results indicated that the PET examination in epilepsy provides valuable information about the location of epileptic focus, and that the findings on PET in patients with partial epilepsy may be one of the good indicators about the intractability of partial epilepsy, and that PET and MRI provide complementary information in the diagnosis of epilepsy.     

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.     

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.     

18FDG-PET in epilepsies of infantile onset with pharmacoresistant generalised tonic-clonic seizures

AIMS: To investigate the pathophysiology of pharmacoresistant epilepsies with cryptogenic generalised tonic-clonic seizures (GTCS) from infancy. METHODS: 18F-Deoxy-Glucose-Positron Emission Tomography 18FDG-PET) with statistical parametric mapping (SPM). Inclusion criteria were: pharmacoresistant chronic epilepsy with GTCS commencing in infancy, no focal seizures except alternating hemiconvulsions and no focal epileptic discharges in the EEG during the first year of the disease, no focal changes upon routine neuroradiological investigations, no indication of brain damage according to history and clinical examination. RESULTS: 15 boys and 15 girls with a mean age of 6.4 years (range l-14 years) were included. All still suffered from seizures despite past treatment with a mean of five drugs. Nearly all were mentally retarded, 19 to a severe and 10 to a minor degree. Fifteen were ataxic and 11 hypotonic. The EEG in 23 showed irregular generalised spike-wave discharges. PET SPM analysis revealed bioccipital hypometabolism related to sedation. Pathological monofocal hypometabolic areas were found in three, multifocal hypometabolic areas in 22 and diffuse bilateral hypometabolism in three patients. Frontal hypometabolism correlated to the degree of mental retardation, hypotonia, and ataxia. Temporomesial hypometabolism correlated to the occurrence of obtunded states and prominent delta rhythms in the EEG. Central and parietal changes were associated with the occurrence of myoclonic seizures and spike-wave discharges. CONCLUSIONS: 18FDG-PET in many of these children with cryptogenic generalised epilepsies showed multifocal hypometabolic areas of unknown aetiology. Primary cortical microdysgenesis and secondary changes due to the severe and long-standing epilepsy must be considered. Only a minority of patients showed restricted focal hypometabolism as a possible indication for surgical treatment.     

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.     

Comparison of the intracarotid amobarbital procedure and interictal cerebral 18-fluorodeoxyglucose positron emission tomography scans in refractory temporal lobe epilepsy.

The relationship between interictal focal hypometabolism determined by 18-fluorodeoxyglucose positron emission tomography (FDG-PET) scans and memory function with the intracarotid amobarbital procedure (IAP) was evaluated in 23 patients with temporal lobe epilepsy. All patients underwent prolonged EEG/video monitoring. The epileptogenic focus was defined by interictal epileptiform discharges and ictal onsets. All 23 patients had recorded seizures arising exclusively from one temporal lobe. PET showed temporal lobe hypometabolism ipsilateral to the epileptogenic focus in 86% (20 of 23) of patients; IAP showed impaired memory of the hemisphere of seizure onset in 65% (15 of 23). Sixty-five percent (13 of 20) of patients with focal hypometabolism had ipsilateral memory impairment. Memory impairment contralateral to the hypometabolic zone was not observed. Ninety-five percent (22 of 23) of patients demonstrated functional impairment by either PET or IAP (or both) on the epileptogenic side.     

Drug-induced changes in cerebral glucose consumption in bifrontal epilepsy

PURPOSE: Positron emission tomography (PET) using 18F-radiolabeled deoxyglucose (18F-FDG) is a sensitive procedure for detection of epileptogenic foci. Although alterations in glucose consumption are not restricted to the area of seizure generation itself, the magnitude and extent of cerebral metabolic disturbances induced by epileptic discharges can be detected. Despite two decades of epilepsy research using 18F-FDG-PET, little is known about the metabolic changes during therapy of focal epilepsy. We report on a child with frontal epilepsy with severe glucose hypometabolism that was nearly completely normalized during drug therapy. METHODS: Interictal 18F-FDG-PET was performed at the onset of epilepsy and after optimized drug therapy in a 5-year-old boy with behavioral abnormalities and repetitive seizures of frontal origin with bifrontal interictal EEG slowing for 8 weeks. Both scans were anatomically matched; initial and intratherapeutic glucose metabolism were compared. RESULTS: In accordance with the epileptogenic focus as identified by EEG and ictal/interictal perfusion single-photon emission tomography (SPECT), bifrontal hypometabolism was depicted by 18F-FDG-PET. Magnetic resonance imaging (MRI) was unremarkable. After dual-drug therapy (valproate, carbamazepine), the boy became seizure free, and his initial behavioral deficits disappeared. A control PET study after 3 months of therapy showed restored glucose consumption; the frontal EEG slowing was normalized. CONCLUSIONS: This case demonstrates that reduction of glucose metabolism in epileptogenic foci may be a result of reversible neuronal dysfunction that correlates with the electroclinical follow-up.     

Objective 3D surface evaluation of intracranial electrophysiologic correlates of cerebral glucose metabolic abnormalities in children with focal epilepsy

To determine the spatial relationship between 2‐deoxy‐2[¹⁸F]fluoro‐D‐glucose (FDG) metabolic and intracranial electrophysiological abnormalities in children undergoing two‐stage epilepsy surgery, statistical parametric mapping (SPM) was used to correlate hypo‐ and hypermetabolic cortical regions with ictal and interictal electrocorticography (ECoG) changes mapped onto the brain surface. Preoperative FDG‐PET scans of 37 children with intractable epilepsy (31 with non‐localizing MRI) were compared with age‐matched pseudo‐normal pediatric control PET data. Hypo‐/hypermetabolic maps were transformed to 3D‐MRI brain surface to compare the locations of metabolic changes with electrode coordinates of the ECoG‐defined seizure onset zone (SOZ) and interictal spiking. While hypometabolic clusters showed a good agreement with the SOZ on the lobar level (sensitivity/specificity = 0.74/0.64), detailed surface‐distance analysis demonstrated that large portions of ECoG‐defined SOZ and interictal spiking area were located at least 3 cm beyond hypometabolic regions with the same statistical threshold (sensitivity/specificity = 0.18–0.25/0.94–0.90 for overlap 3‐cm distance); for a lower threshold, sensitivity for SOZ at 3 cm increased to 0.39 with a modest compromise of specificity. Performance of FDG‐PET SPM was slightly better in children with smaller as compared with widespread SOZ. The results demonstrate that SPM utilizing age‐matched pseudocontrols can reliably detect the lobe of seizure onset. However, the spatial mismatch between metabolic and EEG epileptiform abnormalities indicates that a more complete SOZ detection could be achieved by extending intracranial electrode coverage at least 3 cm beyond the metabolic abnormality. Considering that the extent of feasible electrode coverage is limited, localization information from other modalities is particularly important to optimize grid coverage in cases of large hypometabolic cortex. Hum Brain Mapp 38:3098–3112, 2017. © 2017 Wiley Periodicals, Inc.     

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Several reports have indicated that cortical resection is effective in alleviating intractable epilepsy in children with tuberous sclerosis complex (TSC). Because of the multitude of cortical lesions, however, identifying the epileptogenic tuber(s) is difficult and often requires invaise intracranial electroencephalographic (EEG) monitoring. As increased concentrations of serotonin and serotonin-immunoreactive processes have been reported in resected human epileptic cortex, we used α-[¹¹C]methyl-L-tryptophan ([¹¹C]AMT) position emission tomography (PET) to test the hypothesis that serotonin synthesis is increased interictally in epileptogenic tubers in patients with TSC. Nine children with TSC and epilepsy, aged 1 to 9 years (mean, 4 years 1 month), were studied. All children underwent scalp video-EEG monitoring, PET scans of glucose metabolism and serotonin synthesis, and EEG monitoring during both PET studies. [¹¹C]AMT scans were coregistred with magnetic resonance imaging and with glucose metabolism scans. Whereas glucose metabolism PET showed multifocal cortical hypometabolism corresponding to the locations of tubers in all 9 children, [¹¹C]AMT uptake was increased in one tuber (n = 3), two tubers (n = 3), three tubers (n = 1), and four tubers (n = 1) in 8 of the 9 children. All other tubers showed decreased [¹¹C]AMT uptake. Ictal EEG data available in 8 children showed seizure onset corresponding to foci of increased [¹¹C]AMT uptake in 4 children (including 2 with intracranial EEG recordings). In 2 children, ictal EEG was nonlocalizing, and in 1 child there was discordance between the region of increased [¹¹C]AMT uptake and the region of ictal onset on EEG. The only child whose [¹¹C]AMT scan showed to no regions of increased uptake had a left frontal seizure focus on EEG; however, at the time of his [¹¹C]AMT PET scan, his seizures had come under control. [¹¹C]AMT PET may be a powerful tool in differentiating between epileptogenic and nonepileptogenic tubers in patients with TSC.