Faculty Bibliography

Although functional imaging with positron emission tomography (PET) and single-photon emission computed tomography are useful in the clinical evaluation of intractable epilepsy, these techniques have not been widely applied to understanding the basic mechanisms of the epilepsies. Among patients with infantile spasms, PET studies with 2-deoxy-2[18F]fluoro-D-glucose (FDG) suggest that the spasms are the result of secondary generalization from cortical foci and that maturational factors result in the recruitment of basal ganglia and brainstem serotonin mechanisms that lead to secondary generalization and the unique semiology of the spasms. Attempts to develop an animal model of infantile spasms have not been successful. Glucose utilization studies in the Lennox-Gastaut syndrome also indicate cortical lesions and further suggest that the electroencephalographic pattern of 1 to 2.5 Hz spike-wave activity (slow spike-wave pattern) is an interictal phenomenon. There is a remarkable consistency between 14C-2-deoxyglucose autoradiographic findings and PET observations of glucose utilization performed for patients in the ictal, interictal, and postictal states. Although three patterns of ictal glucose hypermetabolism have been described, hypermetabolism also can be seen in the postictal and interictal clinical states and in various animal models. Preliminary studies of benzodiazepine receptor binding with PET have found that the cortical epileptic region of decreased binding is smaller than the region of hypometabolism on glucose utilization studies, but detailed electrophysiologic comparisons have not been made. Development of new PET methods for the study of presynaptic and postsynaptic neurotransmitter functions will offer unique opportunities in the study of epileptic mechanisms.

Several reports have indicated that cortical resection is effective in alleviating intractable epilepsy in children with tuberous sclerosis complex (TSC). Because of the multitude of cortical lesions, however, identifying the epileptogenic tuber(s) is difficult and often requires invasive intracranial electroencephalographic (EEG) monitoring. As increased concentrations of serotonin and serotonin-immunoreactive processes have been reported in resected human epileptic cortex, we used alpha-[11C]methyl-L-tryptophan ([11C]AMT) positron emission tomography (PET) to test the hypothesis that serotonin synthesis is increased interictally in epileptogenic tubers in patients with TSC. Nine children with TSC and epilepsy, aged 1 to 9 years (mean, 4 years 1 month), were studied. All children underwent scalp video-EEG monitoring, PET scans of glucose metabolism and serotonin synthesis, and EEG monitoring during both PET studies. [11C]AMT scans were coregistered with magnetic resonance imaging and with glucose metabolism scans. Whereas glucose metabolism PET showed multifocal cortical hypometabolism corresponding to the locations of tubers in all 9 children, [11C]AMT uptake was increased in one tuber (n=3), two tubers (n=3), three tubers (n=1), and four tubers (n=1) in 8 of the 9 children. All other tubers showed decreased [11C]AMT uptake. Ictal EEG data available in 8 children showed seizure onset corresponding to foci of increased [11C]AMT uptake in 4 children (including 2 with intracranial EEG recordings). In 2 children, ictal EEG was nonlocalizing, and in 1 child there was discordance between the region of increased [11C]AMT uptake and the region of ictal onset on EEG. The only child whose [11C]AMT scan showed no regions of increased uptake had a left frontal seizure focus on EEG; however, at the time of his [11C]AMT PET scan, his seizures had come under control. [11C]AMT PET may be a powerful tool in differentiating between epileptogenic and nonepileptogenic tubers in patients with TSC.

Functional neuroimaging techniques such as positron emission tomography have made it possible to investigate brain metabolism noninvasively during development. Studies have revealed a dynamic period of metabolic maturation and neuronal growth corresponding to the processes of synaptic proliferation and pruning of unused pathways. This physiologic plasticity is believed to be the biological basis for a critical period of learning and emotional development.

Functional neuroimaging data regarding the development of motor organization in normal children and adolescents are virtually unavailable because of ethical concerns. As an alternative approach, we studied child and adult lesion patients, focusing on movement of the hand ipsilateral to the lesion and on brain activations in the contralesional hemisphere. [15O]-water positron emission tomography was performed during rest and sequential finger-thumb tapping in 10 children (aged 6 to 14 years) and 15 adults (aged 18 to 74 years) with unilateral lesion. We expected more distinct activation/deactivation patterns during movement in adults than in children. While there were no group differences in activation of primary and secondary motor cortices, deactivations in nonmotor cortex were significantly more pronounced in adults than in children. This indirectly supports our hypothesis of developmental focalization of cerebral motor control. Activations in the cerebellum and vermis were significantly stronger in the adults than in the children, possibly reflecting normal developmental patterns.

The brain organization for movement in a 20-year-old man with a history of intrauterine or perinatal right middle cerebral artery stroke was studied. [(15)O]-water positron emission tomography demonstrated a normal pattern of activation during finger movement in the right hand. Movement of the hemiparetic left hand was associated with activation in the supplementary motor area bilaterally and in the left premotor cortex. Blood flow increase was observed in the right temporal lobe adjacent to an extensive area of encephalomalacia, suggesting atypical motor function in the temporal lobe.

Positron emission tomography (PET) studies have shown normal or elevated levels of glucose metabolism in neuronal heterotopia, raising the issue of potential participation of heterotopic neurons in cognitive processing. We studied three patients with heterotopic malformations, using [(15)O]water PET and experimental conditions selected according to the location of the malformations. Task performance was associated with blood flow increases of > 17% within the heterotopia in each patient. In two, these occurred in left frontal heterotopia during sentence generation. In the third patient, activations for facial and visuospatial discrimination and picture naming were found in a right posterior heterotopion. Our findings may reflect participation of heterotopia in cognitive function and suggest that heterotopic neurons synapse with neurons in other brain regions.

OBJECTIVE:There is extensive evidence for post-lesional plasticity in the language and motor domains. We examined possible domain-specific differences in reorganizational patterns, hypothesizing that interhemispheric reorganization would be predominantly homotopic for language, but predominantly nonhomotopic for motor control. DESIGN/METHODS:Using oxygen 15-water positron emission tomography, regional cerebral blood flow was studied during rest, listening to sentences, repetition of sentences, and finger tapping of the right hand. Task-specific primary, secondary, and tertiary regions of interest were defined according to the degree of regional involvement in language/motor functions as documented in previous studies. Regional activations were compared within and across functional domains. PATIENTS/METHODS:Nine patients (aged 4-20 years) with unilateral left hemisphere lesion involving both the primary motor and perisylvian language cortices were studied. Two samples of healthy adults were included for additional comparisons. MAIN OUTCOME MEASURE/METHODS:Hemispheric asymmetry of blood flow changes within regions of interest. RESULTS:As predicted, rightward asymmetry of activations in primary and secondary regions was stronger for language than for movement, but the expected inverse difference for tertiary regions (greater rightward asymmetry of motor activations) was not found. Within-domain comparisons showed that for listening to sentences, rightward asymmetry was strongest in primary and weakest in tertiary regions, whereas the inverse differences were found for movement. CONCLUSION/CONCLUSIONS:The findings suggest a greater potential for homotopic interhemispheric reorganization in the language than in the motor domain. Interhemispheric motor reorganization was generally limited.