Faculty Bibliography

BACKGROUND:In children with tuberous sclerosis, the PET tracer alpha[11C]methyl-L-tryptophan (AMT) has been shown to be selectively taken up by epileptogenic tubers, thus allowing differentiation from nonepileptogenic tubers in the interictal state. OBJECTIVE:To determine whether cortical areas showing increased AMT uptake in children without tuberous sclerosis complex with intractable neocortical epilepsy indicate the epileptogenic zone, and to assess the relative contributions of AMT and 2-deoxy-2[18F]fluoro-D-glucose (FDG) PET abnormalities to the localization of epileptogenic cortical regions. METHODS:Areas of increased AMT and decreased FDG uptake were marked objectively as regions with abnormal asymmetry using an in-house written software in 27 children who underwent comprehensive evaluation for resective epilepsy surgery. The marked PET abnormalities were compared to the locations of scalp and subdural EEG epileptiform abnormalities, as well as histology and surgical outcome. RESULTS:Focal cortical increases of AMT uptake were found in 15 patients. The lobar sensitivity (39.0%) of AMT PET for seizure onset was lower, but its specificity (100%) was higher (p < 0.0001) than that of hypometabolism on FDG PET (sensitivity 73.2%, specificity 62.7%). AMT PET abnormalities were smaller than corresponding FDG PET hypometabolic regions (p = 0.002), and increased AMT uptake occurred in two patients with nonlocalizing FDG PET. Histologically verified cortical developmental malformations were associated with increased AMT uptake (p = 0.044). Subdural electrodes adjacent to the area of increased AMT uptake were most often involved in seizure onset. CONCLUSIONS:Focal increase of cortical AMT uptake in children is less sensitive but more specific for the lobe of seizure onset than corresponding FDG PET hypometabolism, and it is often associated with epileptogenic cortical developmental malformations. AMT PET can assist placement of subdural electrodes even when MRI and FDG PET fail to provide adequate localizing information. Cortical areas adjacent to increased AMT uptake should be carefully addressed by intracranial EEG because these regions often show a high degree of epileptogenicity.

PURPOSE/OBJECTIVE:We studied the relation between quantitative interictal subdural EEG data and visually defined ictal subdural EEG findings in children with intractable neocortical epilepsy, and determined whether interictal EEG data are predictive of ictal EEG onset zones. METHODS:Thirteen children (aged 1.2-15.4 years) underwent prolonged intracranial EEG recording, using 48- to 120-channel subdural electrodes. Three distinct 10-min segments of the continuous interictal EEG recording were selected for each patient, and the spike frequency for each channel was determined by using an automatic spike-detection program. Subsequently the average spike frequency of each electrode was compared with ictal assessment (onset, spread, and no early ictal involvement). In addition, 50 distinct interictal spikes were averaged for each patient, and the amplitude and latency after the leading spike (averaged spike showing the earliest peak) were measured for each electrode and analyzed with respect to ictal EEG findings. RESULTS:Reproducibility of the spike-frequency pattern derived from three 10-min segments was high (Kendall's W, 0.85 +/- 0.08). Electrodes showing the highest spike frequency, the highest spike amplitude, and the leading spike were found to be a part of the seizure onset in 13 of 13, 12 of 13, and 10 of 13 cases, respectively. There was significant correlation between ictal assessment and spike frequency as well as spike amplitude. A receiver operating characteristics analysis showed that a cutoff threshold at 14% of the maximal spike frequency resulted in a specificity of 0.90 and a sensitivity of 0.77 for the detection of seizure-onset electrodes. CONCLUSIONS:Quantitative interictal subdural EEG may predict ictal-onset zones in children with intractable neocortical epilepsy.

The progressive nature of Sturge-Weber syndrome is well known, but the mechanisms of focal cortical and subcortical degeneration in this disorder are poorly understood. In the present study, we assessed the structural and functional integrity of gray and white matter in unihemispheric Sturge-Weber syndrome using quantitative magnetic resonance imaging (MRI) volumetry and MRI-based partial volume correction of [18F]fluorodeoxyglucose positron emission tomographic (PET) images. Gray- and white-matter volumes and glucose metabolism were measured in three brain regions (parieto-occipital underneath the angioma, temporal, and frontal) in six children with Sturge-Weber syndrome (two infants, ages 6 and 9 months; four older children, ages 4 to 14 years), all with unilateral parieto-occipital leptomeningeal angiomatosis. The gray-matter volumes ipsilateral to the angioma were smaller in all children, with the posterior regions underneath the angioma the most affected. In the infants, the white-matter volumes were increased in the region of the angioma, whereas in the regions remote from the angioma in the infants and in all regions of the older children, there were large decreases in white-matter volume. The decreases of frontal and temporal white-matter volume were more pronounced than the corresponding gray-matter volume decreases. The PET studies showed severe hypometabolism in the parieto-occipitalregion underneath the angioma in all of the children. However, the two infants showed glucose hypermetabolism in the frontal and temporal cortical gray matter, whereas these regions had relatively preserved metabolism in the older patients. These results demonstrate differential involvement of gray and white matter in Sturge-Weber syndrome. Both structural and functional abnormalities extend well beyond the angioma, indicating widespread abnormalities of growth and development of the affected hemisphere. Furthermore, whereas increased white-matter volume underlying the angioma may be seen in infants, ipsilateral white-matter regions outside the angioma show volume loss both in infants and in older patients. Extensive gray- and white-matter volume loss and hypometabolism ipsilateral to the angioma likely contribute to the frequently observed progressive cognitive dysfunction in these patients, regardless of the extent of the angioma.

Positron emission tomography (PET) is a powerful clinical and research tool that, in the past two decades, has provided a great amount of novel data on the pathophysiology and functional consequences of human epilepsy. PET studies revealed cortical and subcortical brain dysfunction of a widespread brain circuitry, providing an unprecedented insight in the complex functional abnormalities of the epileptic brain. Correlation of metabolic and neuroreceptor PET abnormalities with electroclinical variables helped identify parts of this circuitry, some of which are directly related to primary epileptogenesis, while others, adjacent to or remote from the primary epileptic focus, may be secondary to longstanding epilepsy. PET studies have also provided detailed data on the functional anatomy of cognitive and behavioral abnormalities associated with epilepsy. PET, along with other neuroimaging modalities, can measure longitudinal changes in brain function attributed to chronic seizures as well as therapeutic interventions. This review demonstrates how development of more specific PET tracers and application of multimodality imaging by combining structural and functional neuroimaging with electrophysiological data can further improve our understanding of human partial epilepsy, and helps more effective application of PET in presurgical evaluation of patients with intractable seizures.

Positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) has been shown to be a highly sensitive diagnostic tool to stage, restage, and monitor the progress of various neoplasms. A number of physiological and non-neoplastic conditions, however, also may be associated with focal accumulation of FDG and can cause false-positive results. This work reports a 52-year-old man who had marked FDG accumulation in carcinoid tumor of the distal ileum. The tumor was resected. A follow-up FDG-PET scan one and a half years later revealed intense FDG accumulation in the abdominal periaortic region, suggesting recurrent malignancy. Computerized tomography (CT) of the abdomen showed soft tissue mass surrounding the aorta. Fine-needle aspiration biopsy of the periaortic soft tissue confirmed benign retroperitoneal fibrosis. This case shows that retroperitoneal fibrosis can cause intense FDG accumulation giving false impression of malignancy. In interpretation of whole-body FDG-PET, various physiological and benign causes of FDG accumulation must be considered in order to avoid pitfalls. The authors have reviewed the literature and discussed association of carcinoid tumor and retroperitoneal fibrosis.

The basis for cognitive impairment in Duchenne muscular dystrophy (DMD) is not well understood but may be related to abnormal expression of dystrophin in brain. The aim of this study was to determine whether regional brain glucose metabolism is altered in children with DMD and whether such metabolic disturbances are localized to regions shown to be normally rich in dystrophin expression. Ten boys (mean age, 11.8 years) with DMD and 17 normal adults as a control group (mean age, 27.6 years) underwent 2-deoxy-2[(18)F]fluoro-D-glucose positron emission tomography (PET) and neuropsychological evaluation. The PET data were analyzed by statistical parametric mapping (SPM). The SPM analysis showed five clusters of decreased glucose metabolism in children with DMD, including the medial temporal structures and cerebellum bilaterally and the sensorimotor and lateral temporal cortex on the right side. At the voxel level, significant glucose hypometabolism was found in the right postcentral and middle temporal gyri, uncus, and VIIIB cerebellar lobule, as well as in the left hippocampal gyrus and cerebellar lobule. The neuropsychological profile of the DMD group revealed borderline nonverbal intellectual functioning, impaired manual dexterity bilaterally, borderline cognitive functioning, and internalizing behavioral difficulties. Our findings demonstrate region-specific hypometabolism, as well as cognitive and behavioral deficits in DMD children. As the regions showing hypometabolism on PET include those normally rich in dystrophin expression, it will be important to determine whether the hypometabolic regions also show cytoarchitectural abnormalities related to the lack of dystrophin.