Elsevier

Molecular Imaging & Biology

Volume 4, Issue 5, September–October 2002, Pages 338-351
Molecular Imaging & Biology

Reviews
Positron Emission Tomography and Epilepsy

https://doi.org/10.1016/S1536-1632(02)00071-9Get rights and content

Abstract

Purpose: This review examines the current role of positron emission tomography (PET) in the investigation and management of patients with epilepsy.

Procedures: A literature review utilizing MEDLINE® and other sources was undertaken. For the comparison of the accuracy of PET with magnetic resonance imaging (MRI) for seizure focus localization, only publications since 1994 were examined. Individual patient data was tabulated to provide figures for seizure focus localization rates for different types of focal epilepsy and the prognostic value of PET findings for epilepsy surgery outcome.

Results: The majority of PET studies used 2-deoxy-2-[18F]fluoro-D-glucose (FDG). The epileptogenic sites typically show reduced FDG uptake (hypometabolism). In patients with intractable temporal lobe epilepsy (TLE), unilateral temporal lobe hypometabolism (UTH) corresponding to the seizure focus was seen in 86% of patients. In the same population, MRI demonstrated relevant abnormalities in 76%. UTH contralateral to the seizure focus was rarely seen (3%). Following temporal lobectomy, 86% of patients with ipsilateral UTH had a good outcome. When MRI was normal, UTH predicted a good outcome in 82%. Fifty percent with bitemporal hypometabolism had independent bilateral foci, and in those who proceeded to surgery only 50% had a good result. In extratemporal epilepsy, hypometabolism relevant to the focus was seen in 67% but, as in TLE, it was often more extensive than pathological abnormality. Recently evidence of a role for 11C-Flumazenil has emerged with reduced binding in the primary epileptogenic site. 11C-Flumazenil abnormalities appear more restricted to abnormal cortex and may be a better guide to the extent of resection required for surgical success.

Conclusions: FDG-PET has a key role in the evaluation of patients with intractable partial epilepsy, particularly when surgery is a treatment option. Development and application of more specific biochemical probes may further improve the clinical value of PET for the understanding and treatment of epilepsy. (Mol Imag Biol 2002;4:338–351)

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

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      Citation 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).

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