Faculty Bibliography

PURPOSE/OBJECTIVE: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 an ictal PET scan demonstrating unilateral frontal cortex hypermetabolism surrounded by hypometabolism. Additional hypometabolic 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.

We describe the tracer kinetic analysis of [C-11]-labeled alpha-methyl-tryptophan (AMT), an analogue of tryptophan, which has been developed as a tracer for serotonin synthesis using positron emission tomography (PET) in human brain. Dynamic PET data were acquired from young healthy volunteers (n = 10) as a series of 22 scans covering a total of 60 minutes and analyzed by means of a three-compartment, four-parameter model. In addition, functional images of the K-complex were created using the Patlak-plot approach. The application of a three-compartment model resulted in low identifiability of individual k-values, especially that of k3. Model identifiability analysis using a singular value decomposition of the final sensitivity matrix showed parameter identifiability to increase by 50% when the Patlak-plot approach was used. K-complex values derived by the Patlak-plot approach overestimated the compartmental values by 10 to 20%, because of the violation of the dynamic equilibrium assumption. However, this bias was fairly constant in all structures of the brain. The rank order of K-complex values from different brain regions corresponded well to the regional concentrations of serotonin in human brain (P < 0.0001). These results indicate that the Patlak-plot method can be readily applied to [C-11]AMT data in order to create functional images of the K-complex, reflecting serotonin synthesis rate, within an acceptable error margin.

We evaluated the clinical role of positron emission tomography (PET) in 23 children with tuberous sclerosis complex. Mean age of the children when first scanned was 3.3 years. Mean age when seizures began was 8.7 months. All, except three, were at least mildly developmentally delayed. PET images were visually analyzed and compared to computed tomography (CT), magnetic resonance imaging (MRI), and the electroencephalogram (EEG). In two infants, interictal PET study was normal. One of the studies was performed with a low resolution early generation scanner at age 7 months; the other infant was 2 days old. Twenty-one of the 23 children had focal or multifocal cortical hypometabolism. Some hypometabolic cortical regions on PET did not show corresponding abnormalities on CT and MRI, and may be due to epileptogenic mechanisms or small tubers. PET provides additional localizing information to CT and MRI in patients with tuberous sclerosis complex. However, because of the normally low cerebral glucose metabolism in infancy, PET may give false negative findings if performed prior to about 1 year of age. The usefulness of glucose metabolism PET in most patients with tuberous sclerosis complex is limited. However, if the EEG, CT, and MRI abnormalities are unifocal or unilateral, and surgery is being contemplated, more detailed evaluation with PET may help to determine if contralateral tubers are present and evaluate the functional integrity of the brain as a whole.

Positron Emission Tomography (PET) with 2-deoxy-2 [18F]-fluoro-D-glucose provides a measure of functional brain activity, particularly in the dendritic field. In CLN3 (juvenile neuronal ceroid lipofuscinosis or juvenile Batten disease, with fingerprint inclusions) hypometabolism slowly spreads from calcarine to anterior areas, sparing subcortical structures and brainstem. In CLN2 (late infantile neuronal ceroid lipofuscinosis or Jansky-Bielschowsky disease, with curvilinear inclusions) degeneration is rapid with generalized cortical and subcortical hypometabolism. This is associated with rapidly progressive cerebral atrophy on anatomical neuroimaging. A 4-year-old child with CLN2 scanned with PET 13 months after the clinical onset showed hypometabolism, severe in the thalamus and mild in cortical areas. Three other patients with CLN2 had severe generalized hypometabolism and brain atrophy. Longitudinal PET studies in CLN may provide key insights into degenerative processes.