Faculty Bibliography

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.

Functional maturation of human cerebellar structures was previously difficult to evaluate with positron emission tomography (PET) because of scanner resolution. Only vermis and cerebellar hemispheres could be reliably identified with 2-deoxy-2[18F]fluoro-D-glucose (FDG) PET. In the present study, we have used a new high resolution PET system, the Siemens EXACT-HR, to study, in depth, the patterns of glucose metabolism in various cerebellar structures. Due to the orientation of the cerebellar fissures which are important landmarks, the largest number of regions could be identified when the cerebellar regions were displayed on coronal planes. The high resolution PET images, together with magnetic resonance imaging (MRI) data and standard atlases, now allow identification of the following cerebellar structures: anterior vermis, posterior vermis, dentate nucleus, anterior lobe, posterior quadrangular lobule, superior semilunar lobule, inferior semilunar, gracile, and biventer lobules, tonsil, and cerebellar white matter. These cerebellar regions are displayed in an atlas format together with magnetic resonance images to allow easy identification. The present study is a prerequisite for detailed PET analyses of cerebellar metabolism in children with diseases of the cerebellum.

Alpha-[11C]methyl-L-tryptophan (AMT) has been synthesized by stereoselective methylation with [11C]methyl iodide of the lithium-enolate generated by treating dimethyl 2(S), 3a(R), 8a(S)-(+)-hexahydro-8(phenylsulfonyl)pyrrolo [2, 3-b]indole-1,2-dicarboxylate (2) with lithium diisopropyl amide (LDA) at -55 degrees C, followed by ring opening using trifluoroacetic acid and alkaline hydrolysis of the protecting groups. The crude product was purified by a simple reverse-phase C-18 Sep-Pak procedure. The purified product was isolated with an average radiochemical yield of 53 +/- 12% (decay corrected) in 30-35 min from [11C]methyl iodide. At end of synthesis (EOS), 138 +/- 35 mCi (n = 24) of product was collected with a specific activity of ca. 1-1.3 Ci/mumol (EOS) (4-5 Ci/mumol @ EOB) starting from 1.5 Ci (EOB) of [11C]CO2.

This prospective case study examined social communication (i.e., formal thought disorder, cohesion), language, positron emission tomography glucose utilization, and neuropathology in four children with Rasmussen encephalitis who achieved seizure control following right hemispherectomy. Prior to hemispherectomy, all four children had illogical thinking, loose associations, cohesive deficits, and impaired performance on formal language tests. Their postoperative improvement in social communication and language appeared to be related to age of onset, duration of illness, and postsurgical reversibility of hypometabolism in the nonresected prefrontal cortex. These changes were not associated with increase in IQ scores. The variability in the type and extent of pathologic change across subjects reflected the severity and duration of the illness. The study's findings imply that early surgical intervention might have mitigated certain aspects of the social communication and linguistic deficits found in these children.

Developmental brain plasticity in association with focal brain injury is dependent on a number of factors, including age of the individual at the time of injury, size and topography of the brain lesion, maturational state of the brain system injured, integrity of brain areas surrounding and contralateral to the lesion, presence and duration of epilepsy, and medication effects. Recently developed functional neuroimaging tools now make it possible to study non-invasively several aspects of human brain functional reorganization in response to injury. Clinical models which are suitable for the study of developmental brain plasticity include patients who have undergone cortical resections for the alleviation of intractable epilepsy, patients who have sustained unilateral cerebrovascular insults at various periods of development, patients with chronic progressive unilateral brain injury such as in the Sturge-Weber syndrome, and patients with early sensory deprivation such as blind or deaf subjects. Although evidence of functional brain reorganization can be demonstrated in these models, it is emphasized that the neurobiological rules that govern intrahemispheric versus interhemispheric reorganization of function in the brain are, at present, poorly understood.

Fifty-eight children who underwent anatomical, functional, or modified anatomical hemispherectomy for intractable seizures from 1986 to 1995 were evaluated for seizure control, motor function, and complications. Age at surgery ranged from 0.3 to 17.3 years (median 2.8 years). Twenty-seven anatomical, 27 functional, and 4 modified anatomical hemispherectomies were performed. Seizure control and motor function in the 50 patients with more than 1 year follow-up revealed a 90% or better reduction in seizure frequency in 44/50 (88%) overall: 19/22 (86%) anatomical, 23/26 (89%) functional, and 2/2 modified anatomical. Motor function of the preoperatively hemiparetic extremities was improved or unchanged postoperatively in 38/50 (76%) of the patients. Complications included one intraoperative death, one late death from shunt obstruction managed elsewhere, late postoperative seizure breakthrough requiring reoperation and further disconnection in 5/27 functional hemispherectomy patients, mild cerebrospinal fluid infections in 3/27 anatomical hemispherectomy patients, and hydrocephalus requiring shunting in 3/27 functional hemispherectomy patients. A review of the literature and comparison of techniques is presented.