Faculty Bibliography

Infantile spasms most commonly show symmetric behavioral and electroencephalogram (EEG) manifestations. Asymmetric and asynchronous behavioral spasms occur occasionally, but their relationship to ictal EEG and to other localizing studies has not received much attention. We reviewed 75 consecutive video-EEG recordings, done at UCLA from 1982 to 1992, that contained infantile spasms; 8,680 spasms were scored for behavioral and EEG asymmetry and asynchrony. Of the recorded spasms, 25% were asymmetric and 7% were asynchronous. Most asymmetric of asynchronous spasms were associated with an ictal EEG discharge that was contralateral to the behaviorally more involved side. In 12 of the 60 patients (20%), more than half of the recorded spasms were asymmetric of asynchronous. Baseline EEG, magnetic resonance imaging, positron emission tomography, and neurological examination revealed structural and functional brain abnormalities that involved the contralateral central region significantly more often in the children with > 50% spasm asymmetry or asynchrony than in the other children. Partial seizures with lateralized motor behavior also occurred frequently in these children. The findings suggest that asymmetric and asynchronous spasms are generated by a cortical epileptogenic region that involves the primary sensorimotor area. The combination of asymmetric and asynchronous infantile spasms, partial motor seizures involving the same side of the body, and pathology in the contralateral central region may represent a unique subset of symptomatic localization-related infantile epilepsy.

PET is an additional tool in the armamentarium to provide improved care to children and infants with epilepsy. It provides important lateralizing information noninvasively, thus avoiding the need for depth or subdural electrodes in most instances. It can be invaluable when CT and MR imaging do not show a structural lesion. When it corresponds to an EEG focus of epileptogenicity, intraoperative electrocorticography may be used to delineate further the extent of surgical resection, often with impressive reduction in the seizure frequency postoperatively. As PET technology continues to improve, the clinical role of PET in the future will undoubtedly continue to grow.

Three females in 2 families were originally diagnosed with Spielmeyer-Vogt disease (SVD). The clinical course was different from SVD, with vision well preserved until age 10 years, and learning rather than visual difficulties the marker at the onset. Later, regression was unusually rapid, including global dementia, blindness, aphasia, and finally loss of self-feeding and ambulation between ages 12-18 years. MRI scan in patient 3 documented brain atrophy between ages 8-10 years. Position Emission Tomography (PET) scanning with fluorodeoxyglucose in patients 2 and 3 showed diffusely decreased or absent cortical glucose metabolism, comparable at ages 12 and 18 years, respectively, to the results found in the oldest typical SVD case tested at age 29 years. Fine granular inclusions, instead of the expected fingerprint inclusions, were demonstrated by electron microscopy of lymphocytes, conjunctiva, and skin. Usual markers on chromosome 16p12 were not present in the first family tested. The clinical course, with nonspecific initial behavior difficulties, late onset of visual decline followed by fast global regression, progressive brain atrophy, decreased cortical glucose utilization as shown by PET scanning, and granular tissue inclusions, suggest a genetic variant of SVD.

The present positron emission tomography study used 2-deoxy-2[18F]fluoro-D-glucose to examine age-related changes in local cerebral metabolic rates for glucose (LCMRglc) in sedated rhesus macaques and vervet monkeys. Nineteen vervet monkeys were scanned in a cross-sectional design, which consisted of three age groups (birth to 59 d, 60-179 d, 180 d to adult) that captured the developmental period of greatest synaptic density within the second group. Two rhesus and two vervet monkeys were also examined longitudinally. Subjects were sedated throughout the procedure with a combination of ketamine and midazolam. Longitudinal and cross-sectional analyses of 20 brain regions indicated lowest LCMRglc in rhesus and vervet monkeys < 2 months of age (about 60% of adult levels). These metabolic rates more than doubled to approximately 155% of adult levels after the second postnatal month, coincident with transient synaptic overproduction and increased sociobehavioral activity. LCMRglc remained high until 6 months postnatally, coincident with continued dendritic growth and the emerging sociobehavioral independence of the young monkey. After 6 months, LCMRglc decreased gradually to adult levels. Thus, the period between 2 and 6 months is a time of peak metabolic activity, which coincides with increased histologic and behavioral activity in the developing monkey.

The recent intense focus of attention on further characterization and management of infantile spasms is due, in part, to the resistant nature of these seizures and the frequently poor cognitive outcome, even when the seizures are controlled. Technological advances have increased our ability to diagnose specific brain disorders associated with infantile spasms, and have led to new therapeutic approaches. Most infantile spasms previously classified as cryptogenic have now been shown to be associated with various types of brain malformations and can, therefore, be reclassified as symptomatic. Infantile spasms are probably initiated by cortical epileptic discharges which propagate to the brainstem and other subcortical areas. When the epileptogenic cortex is unilateral in an infant with resistant spasms, resective surgery may be considered. For most infants, however, surgery is not a viable option, and the search for the most effective and least toxic anticonvulsant continues.

The Landau-Kleffner syndrome is sometimes associated with continuous spike-waves during slow-wave sleep. The clinical significance of this association is unclear. In order to investigate differences in glucose metabolic patterns between awake and sleep states in two children with Landau-Kleffner syndrome and continuous spike-waves during slow-wave sleep, fluorodeoxyglucose positron-emission tomographic (PET) studies were performed in each state. In the first patient, the awake interictal PET study revealed moderate hypometabolism in the thalamus and frontal and temporal cortex and mild hypometabolism in the parietal and anterior cingulate cortex bilaterally. Occipital cortex was severely hypometabolic bilaterally. In a repeat PET study performed during sleep in which continuous spike-waves during slow-wave sleep were present, the only difference noted compared to the awake study was a marked bilateral increase in temporal cortex metabolism. The awake interictal PET in the second child was normal, except for mildly increased relative glucose metabolism in the left inferior temporal cortex. The sleep PET study with continuous spike-waves during slow-wave sleep in this child showed hypermetabolism in both temporal lobes; however, this was more pronounced, with a wider distribution in the left temporal cortex. In normal subjects, PET studies performed during awake and sleep states have not revealed such differences. Whether the temporal lobes are involved in the generation of continuous spike-waves during slow-wave sleep remains to be confirmed in a larger group of patients. The first child was treated surgically with multiple subpial transection, following which continuous spike-waves during slow-wave sleep disappeared and language function improved.(ABSTRACT TRUNCATED AT 250 WORDS)