Faculty Bibliography

Positron emission tomography (PET) with 2-deoxy-2[18F]fluoro-D-glucose (FDG) was used to study 9 children who demonstrated complete or partial agenesis of the corpus callosum (ACC) on magnetic resonance imaging (MRI). Of the 7 patients with epilepsy, FDG-PET clearly localized areas of cortical metabolic abnormality in 6 patients; in 5 of these, localization of the metabolic abnormalities on PET corresponded to electroencephalographic localization of epileptogenicity. MRI documented focal cortical abnormalities in only 2 of the 7 children with epilepsy. In 1 patient, the abnormality observed on MRI was confined to a frontal lobe, whereas the FDG-PET study revealed hypometabolism of the entire hemisphere. One patient with infantile spasms exhibited bilateral multifocal epileptiform discharges on electroencephalography, whereas both the PET and MRI revealed only left hemispheral cortical abnormalities. Another patient with infantile spasms had prominent brainstem glucose metabolic activity on FDG-PET in the absence of any MRI or PET cortical abnormality. Two children underwent surgery because of refractory seizures; the resected cortical tissue in both patients consisted of cortical microdysgenesis. Seizure control improved significantly in both patients. FDG-PET studies in the 2 highest functioning patients (i.e., only minor learning disabilities and no epilepsy) did not reveal any focal cortical hypometabolism; therefore, there appears to be an association between the presence of focal metabolic abnormalities on PET and the presence of seizures in ACC patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Male Sprague-Dawley rats received either naloxone (75 micrograms/h) or saline (0.5 microliter/h) s.c. for 14 days delivered with osmotic minipumps. Two days after termination of either treatment, daily amygdala kindling stimulation was applied until the animals experienced stage V kindled seizures. Benzodiazepine (BDZ) binding sites were labeled with [3H]flunitrazepam (2 nM), and changes in specific brain areas were determined by in vitro quantitative autoradiography. Twenty-four hours after the last electrical stimulation, the saline pretreated fully kindled rats showed enhanced BDZ receptor binding in dentate gyrus, and decreased binding in cingulate cortex ipsilateral to the stimulation compared to saline controls. Twenty-eight days after the last stage V kindled seizure, the significant alterations were no longer evident. In agreement with a previous study, we found that naloxone pretreated amygdala kindled rats showed stage V kindled seizures followed by intervals of 3-5 days in which the same electrical stimulation failed to induce any behavioral and EEG alterations. In comparison with the saline pretreated kindled and saline control groups, the naloxone pretreated kindled rats had significantly higher BDZ binding in different cortical areas, amygdala complex, hippocampus, substantia nigra and periaqueductal gray, 24 h after the last electrical stimulation. The present study indicates that previous chronic exposure to naloxone increases BDZ receptor binding in kindled rats, and suggests that this effect may be associated with the enhanced seizure suppression observed in these animals.

Transforming growth factor alpha (TGF alpha) is a mitogenic polypeptide which acts at the epidermal growth factor receptor to produce its biologic effects. Recent studies have demonstrated that TGF alpha may act as a neurotrophic factor. Cerebral hemispherectomy (hemidecortication) is performed on some children with intractable epilepsy. Prior studies have demonstrated improved functional recovery in both children and animals when the surgery is performed at a very early age. In order to test whether TGF alpha may be involved in the functional recovery of the neostriatum following cerebral hemidecortication, we performed in situ hybridization for TGF alpha mRNA on brains of rats which underwent hemispherectomy at postnatal day (P) 6 or P12 or in adulthood, and sacrificed one, 7, or 30 days following surgery. Normal striatal expression in control animals was very high at P6 and then decreased throughout development. In animals undergoing lesion at earlier ages (P6 and P12), TGF alpha mRNA expression was first depressed in the ipsilateral neostriatum one day after surgery and then elevated to supranormal levels 7 and 30 days after surgery. Maximal decreases (40% below contralateral neostriatum) were seen in animals lesioned at P12 and sacrificed the next day. Maximal elevations (60% greater than opposite neostriatum) were seen in animals operated on at P6 and sacrificed 30 days post surgery. Expression in the adult animal was only mildly affected, with a 20% increase found in the ipsilateral caudate 7 days after the lesion, but no significant changes after one or 30 days survival.(ABSTRACT TRUNCATED AT 250 WORDS)

This study examined the presurgical 2-deoxy-2[18F]-fluoro-D-glucose positron emission tomography (PET) patterns of regional cerebral glucose metabolism in the non-resected hemisphere of 13 children who underwent hemispherectomy for early-onset intractable seizures. These patterns were compared with the rate of change in the children's non-verbal communication scores, measured before and after surgery. Irrespective of the side of surgery, the pre-operative glucose metabolism in the non-resected prefrontal cortex correlated significantly with the postoperative rate of change in the children's ability to focus the attention of an adult on an object or event (joint attention). These preliminary findings suggest that pre-operative PET patterns might be associated with certain aspects of the developmental outcome of children undergoing hemispherectomy.

Recent developments in neuroimaging have advanced our capability to diagnose and perform presurgical evaluations in a large proportion of children without recourse to invasive monitoring techniques. Functional imaging is also providing us with novel insights into the mechanism of certain childhood epileptic syndromes. The role of anatomic (computed tomography, magnetic resonance imaging) and functional (single photon emission computed tomography, positron emission tomography) imaging modalities in the diagnosis and therapeutic decision making in major epileptic syndromes of childhood is reviewed.

Positron emission tomography (PET) is an imaging technique that allows local chemical and physiologic functions in various body organs to be measured. Studies of local cerebral glucose metabolism in infants and children using PET have provided important information on human brain functional development and plasticity. In the neonate, PET studies have provided important clues into the pathophysiology of hypoxic-ischemic injury. Patterns of cerebral glucose utilization in various clinical subtypes of cerebral palsy associated with perinatal brain injury are discussed and contrasted to metabolic patterns seen in cerebral palsy without clear etiology. Expanding PET technology provides a new approach that holds great promise in the diagnosis and management of brain disorders affecting the neonate.