CORTICAL GABA[sub]A[/sub] RECEPTOR BINDING ABNORMALITIES REMOTE FROM THE PRIMARY EPILEPTIC FOCUS: WHAT IS THEIR ELECTROPHYSIOLOGICAL AND CLINICAL SIGNIFICANCE?
Abstract number :
2.397
Submission category :
Year :
2003
Submission ID :
1810
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Csaba Juhasz, Diane C. Chugani, Otto Muzik, Eishi Asano, Aashit Shah, Jagdish Shah, Sandeep Sood, Kenji Kagawa, Krisztina Benedek, Harry T. Chugani Pediatrics, Wayne State University, Detroit, MI; Neurology, Wayne State University, Detroit, MI; Radiology,
In non-lesional epilepsy, accurate presurgical delineation of epileptogenic brain regions is often difficult, but critical for optimal surgical outcome. [11C]Flumazenil (FMZ) PET can identify cortical areas with abnormal gamma-aminobutyric acid[sub]A[/sub] (GABA[sub]A[/sub]) receptor binding, and has been shown to be sensitive for detecting hippocampal and neocortical seizure onset zones. Cortical FMZ binding abnormalities [underline]remote[/underline] from the primary epileptogenic region have also been observed, but their electroclinical significance remains to be clarified.
Twenty-five children (mean age: 7.4 years) with intractable non-lesional epilepsy (in the form of complex partial seizures [n=18] or infantile spasms [n=7]) underwent presurgical evaluation including FMZ PET and chronic intracranial EEG monitoring. Cortical areas with decreased FMZ binding (defined by abnormal asymmetries of small homologous cortical regions) were objectively marked on the side of the epileptic focus, projected on the brain surface reconstructed from the MRI, and correlated to ictal and interictal subdural grid data as well as clinical seizure variables.
Focal decrease of cortical FMZ binding on the side of the epileptic focus was found in 21/25 (84%) patients, and correctly detected the seizure onset zone in 20 (80%). In addition, 23 areas of decreased FMZ binding remote from the primary focus were found and marked in 13 patients, and 20 of these areas were covered by intracranial electrodes. Thirteen (65%) of these 20 remote regions were involved in rapid seizure spread ([lt]10 seconds after seizure onset) and one showed frequent interictal spiking without ictal involvement. In the whole group, patients with remote FMZ abnormality had significantly higher estimated life-time seizure number (a composite value created from epilepsy duration and seizure frequency) than those with only perifocal FMZ PET abnormality (p=0.016; Mann-Whitney U test). In children with complex partial seizures, remote FMZ PET abnormalities were associated with both high seizure frequency (p=0.048) and high life-time number of seizures (p=0.007).
In addition to confirming the high sensitivity of FMZ PET for detecting the seizure onset zone, this study shows that cortex with decreased GABA[sub]A[/sub] receptor binding remote from the primary seizure focus, when present, shows ictal involvement or interictal epileptiform activity on intracranial EEG in 2/3 of patients with non-lesional epilepsy. These regions are not typically obvious on scalp EEG recordings. Thus, FMZ PET impacts clinical management by guiding subdural electrode placement on previously unsuspected epileptogenic regions, which may represent potential secondary epileptic foci.
[Supported by: NIH Grant NS34488]