ReviewsPositron Emission Tomography and Epilepsy
Introduction
Epilepsy, when refractory to medical therapy, is both debilitating for the patient, and costly to the community due to the usual early age of onset and the loss of education and work capacity. It has been estimated that, in the general community, epilepsy has a prevalence of 20–50 cases per 100,000 population and 15% of these patients will be refractory to medication.1 Surgery for medically intractable epilepsy may reduce the frequency of epileptic seizures to the point where normal life activities can be pursued, and may result in total seizure freedom. A recent randomized, controlled trial of surgery for temporal lobe epilepsy found significantly improved seizure control and quality of life with surgical treatment compared to medical treatment alone.2
Improvement in non-invasive seizure focus localization has substantially reduced the need for intracranial electrode studies prior to surgery. Subdural strips and grids and intracranial depth electrodes are now reserved for more difficult cases when non-invasive localization is equivocal or resection is in eloquent cortical areas. Established non-invasive localization techniques include prolonged video-surface electroencephalogram (EEG) monitoring, neuropsychological assessment, magnetic resonance imaging (MRI), positron emission tomography (PET), and ictal single photon emission computed tomography (SPECT). Anatomical neuroimaging with MRI does not identify structural lesions in all patients. Ictal SPECT using cerebral blood flow agents requires hospitalization with reduction in the patient's medication and does not capture the seizure onset in all patients. PET is a functional neuroimaging modality that provides additional localizing data in the interictal state as an outpatient procedure.
PET was first applied to epilepsy two decades ago following the observation of regional glucose hypometabolism in patients with partial seizures using 2-deoxy- 2-[18F]fluoro-D-glucose (FDG).3, 4 PET uniquely can provide both qualitative and quantitative information on cerebral blood flow, oxygen consumption, and cerebral glucose metabolism. It can also measure the binding of specific ligands to receptors, which contribute to the genesis and propagation of seizures. As an outpatient procedure, PET has potential advantages over investigations that are invasive or require an inpatient admission. The major clinical application of PET in epilepsy at present is in the presurgical evaluation of patients with intractable partial seizures. The scientific insights afforded by PET have to some extent advanced our understanding of the pathophysiology of chronic partial epilepsies, but greater knowledge will come from further development of specific biochemical PET probes.
The advance of MRI in the last 10 years has led to changes in the application of PET to epilepsy. Co-registration of PET with MRI allows greater accuracy in anatomical localization of functional lesions and may reveal subtle structural lesions on second look at sites of functional abnormality. Both clinical and research PET need to be interpreted with high quality MRI to provide the best structural-functional correlation.
Section snippets
The Pathophysiology of Altered Cerebral Glucose Metabolism
The majority of PET studies have used FDG in the investigation of temporal lobe epilepsy. Due to its ready availability, our knowledge of FDG-PET in epilepsy has been combined with a large amount of clinical, radiological, electroencephalographic, and pathological data available in this condition. Interictal PET in the partial epilepsies using FDG identifies the cortical area of interictal dysfunction usually as an area of glucose hypometabolism. This functional deficit zone is in close
Mesial Temporal Epilepsy
Temporal lobe epilepsy (TLE) is characterized by simple (somatic or psychic symptoms with preservation of awareness) or complex (with altered awareness) partial seizures or secondarily generalized seizures or a combination of these. Most temporal lobe seizures arise from either the hippocampus or the amygdala in the mesial temporal region, and usually last from 60 to 90 seconds. Common symptoms of the simple partial phase include psychic phenomena such as déjà vu and fear, autonomic features
Imaging of Cerebral Glucose Metabolism Using Interictal FDG-PET in Discrete Pediatric Syndromes
Many of the less common but severely debilitating epilepsy syndromes have been investigated with FDG-PET. The findings reflect the functional disturbances in these conditions, which may not be associated with structural changes as shown by current generation MRI. Examples include West's syndrome (infantile spasms with cognitive decline and characteristic EEG);67 Lennox-Gastaut syndrome (tonic, atonic, and tonic-clonic seizure patterns with characteristic EEG;68, 69, 70 and Landau Kleffner
Benzodiazepine Receptor Imaging
The receptor most studied in the pathogenesis of epilepsy is the benzodiazepine-receptor (BZD), mostly with 11C-flumazenil (FMZ) PET. These receptors are situated on the same macro-molecule as the γ-aminobutyric acid (GABA)-receptor, the most important inhibitory neurotransmitter in the central nervous system. In patients with TLE arising from amygdala/hippocampal regions, a localized reduction of 11C-flumazenil binding in the mesial temporal lobe is seen, in contrast to the more extensive
Effect of Epilepsy Drugs on Glucose Metabolism
Not surprisingly, different antiepileptic drugs have been shown to affect cerebral glucose metabolism to varying degrees, with phenobarbital being a greater depressant (up to 37%) than valproate, carbamazepine, or phenytoin.99, 100, 101 This effect may be related to the cognitive impairment sometimes found in patients on these drugs, and indeed greater cognitive and attentional impairment has been shown to occur with barbiturate treatment than with the other drugs. The physiological basis of
Conclusions
In many centers, FDG-PET plays a key role in the pre-surgical evaluation of patients with intractable partial epilepsy, particularly when standard investigations are inconclusive for the localization of the epileptic focus. Many studies have shown that FDG-PET is the most sensitive imaging modality for the detection of a seizure focus, particularly in temporal lobe epilepsy, and when findings are unilateral, hypometabolism is a good predictor of the success of surgery and low risk of
References (124)
- et al.
Interictal cerebral metabolism in partial epilepsies of neocortical origin
Epilepsy Res
(1991) - et al.
FDG-PET in children and adolescents with partial seizuresrole in epilepsy surgery evaluation
Epilepsy Res
(1995) - et al.
Interictal cerebral metabolism in partial epilepsies of neocortical origin
Epilepsy Res
(1991) - et al.
Positron emission tomographycomparison of clinical utility in temporal lobe and extratemporal epilepsy
J Epilepsy
(1994) - et al.
Statistical parametric mapping of regional glucose metabolism in mesial temporal lobe epilepsy
Neuroimage
(2000) - et al.
Positron emission tomographycomparison of clinical utility in temporal lobe and extratemporal epilepsy
J Epilepsy
(1994) - et al.
HemimegalencephalyEvaluation with positron emission tomography
Pediatr Neurol
(1993) - et al.
Sturge-Weber syndromea study of cerebral glucose utilization with positron emission tomography
J Pediatr
(1989) - et al.
Corpus Callosum Agenesis and EpilepsyPET Findings
Pediatr Neurol
(1994) - et al.
Interictal and postictal focal hypermetabolism on positron emisssion tomography
Pediatr Neurol
(1993)
In vivo demonstration of BZ receptor binding in human epileptic foci
Lancet
Quantification of opiate receptors in two patients with mesiobasal temporal lobe epilepsy, before and after selective amygdalohippocampectomy, using positron emission tomography
Epilepsy Res.
Prevalence of epilepsy in Rochester, Minnesota, 1940–1980
Epilepsia
A randomised, controlled trial of surgery for temporal lobe epilepsy
N Engl J Med
Epileptic patterns of local cerebral metabolism and perfusion in humans determined by emission computed tomography of 18FDG and 13NH3
Ann Neurol
Comparative localization of epileptic foci in partial epilepsy by PCT and EEG
Ann Neurol
Pathological findings underlying focal temporal lobe hypometabolism in partial epilepsy
Ann Neurol
PET and SPECT in Epilepsy
Eur Neurol
Clinical evaluation of interictal fluorine-18-fluorodeoxyglucose PET in partial epilepsy
J Nucl Med
Hippocampal atrophy is not a major determinant of regional hypometabolism in temporal lobe epilepsy
Epilepsia
Correlation of hippocampal neuronal density and FDG-PET in mesial temporal lobe epilepsy
Epilepsia
FDG-PET reveals temporal hypometabolism in patients with temporal lobe epilepsy even when quantitative MRI and histopathological analysis show only mild hippocampal damage
Arch Neurol
Hippocampal volume and glucose metabolism in temporal lobe epileptic foci
Epilepsia:
Postoperative changes in cerebral metabolism in temporal lobe epilepsy
Arch Neurol
Patterns of postictal cerebral blood flow in temporal lobe epilepsyQualitative and quantitative analysis
Neurology
Clinical characteristics of partial seizures
The relative contributions of MRI, SPECT, and PET imaging in epilepsy
Epilepsia
Comparison of (11C)flumazenil and (18F)FDG as PET markers of epileptic foci
J Neurol Neurosurg Psychiatry
11C) Flumazenil binding in the medial temporal lobe in patients with temporal lobe epilepsycorrelation with hippocampus MR volumetry, T2 relaxometry, and neuropathology
Neurology
Localization of Temporal Lobe Epileptic foci with iodine-123 iododexetimide cholinergic neuroreceptor Single-Photon Emission Computed Tomography
Neurology
Neuroimaging in temporal lobe epilepsytest sensitivity and relationships to pathology and post-surgical outcome
Epilepsia
The utility of a 3-dimensional, large-field-of-view, sodium iodide crystal-based PET scanner in the presurgical evaluation of partial epilepsy
J Nucl Med
Focal functional deficits in TLE on PET scans and the intracarotid amobarbital procedure
Epilepsia
Inter-modality comparisons of seizure focus lateralization in complex partial seizures
Eur J Nucl Med
False localisation of temportal lobe epilepsy with FDG positron emission tomography
Epilepsia
Single-voxel proton MR spectroscopy and positron emission tomography for lateralization of refractory temporal lobe epilepsy
Amer J Neuroradiol
The role of positron emission tomography in presurgical evaluation of partial epilepsies of neocortical origin
Quantifying interictal metabolic activity in human temporal lobe epilepsy
J Cereb Blood Flow Metab
Temporal lobe hypometabolism on PETPredictor of seizure control after temporal lobe lobectomy
Neurology
Accurate prediction of postoperative outcome in mesial temporal lobe epilepsya study using PET with F-18 FDG
Arch Neurol
Outcome of temporal lobe epilepsy surgery predicted by statistical parametric PET imaging
J Nucl Med
Postsurgical outcome of patients with uncontrolled complex partial seizures and temporal lobe hypometabolism in F-18 FDG PET
Invest Radiol
Bilateral temporal hypometabolism in epilepsy
Epilepsia
Interictal cerebral metabolism and epilepsy in cavernous angiomas
Brain
Preoperative FDG-PET temporal lobe hypometabolism and verbal memory after temporal lobectomy
Neurology
An interictal study of partial epilepsy using positron emission tomography and the oxygen-15 inhalation technique
J Neurol Neurosurg Psychiatr
Noninvasive functional brain mapping by change-distribution analysis of averaged PET images of H2150 tissue activity
J Nucl Med
Cited by (80)
Brain molecular imaging in pharmacoresistant focal epilepsy: Current practice and perspectives
2018, Revue Neurologique3 Tesla MRI-negative focal epilepsies: Presurgical evaluation, postoperative outcome and predictive factors
2017, Clinical Neurology and NeurosurgeryPresurgical evaluation for drug refractory epilepsy
2016, International Journal of SurgeryPET imaging in extratemporal epilepsy requires consideration of electroclinical findings
2016, Epilepsy ResearchCitation Excerpt :False PET lateralization seems to occur in only one to 3% of the medically refractory TLE patients (Sperling et al., 1995). However, in extratemporal epilepsy (ETE) only 67% show a hypometabolic area matching the extratemporal seizure onset zone and hypometabolism tends to be more widespread commonly involving temporal regions (Casse et al., 2002; Engel, 1991; Salanova et al., 1993; Swartz et al., 1995; Theodore et al., 1983). Results of resective epilepsy surgery, though, depend on the exact localization of the epileptogenic zone, which is typically based on the results of EEG-video monitoring with structural (high-resolution magnetic resonance imaging, MRI), and functional imaging (PET; single-photon emission computed tomography, SPECT, with MRI coregistration, SISCOM analysis) (Engel, 1999; Widdess-Walsh et al., 2007).
Neuroimaging in refractory epilepsy. Current practice and evolving trends
2015, European Journal of Radiology