Faculty Bibliography

We describe a 21-year-old man who developed copper deficiency manifested as a demyelinating neuropathy, chronic intestinal pseudo-obstruction, osteoporosis, testicular failure, retinal degeneration, and cardiomyopathy with a tortuous aorta. His serum copper was low and did not increase despite administration of large doses of intravenous copper sulfate. The ceruloplasmin level as measured by an antibody technique was normal, yet ceruloplasmin (Cp) oxidase activity was very low. The Cp amino acid sequence was normal. This suggests that the copper deficiency was caused by a defect in hepatic processing of copper for incorporation into Cp.

In 3 children who had undergone cerebral hemispherectomy (hemidecortication) between the ages of 1 year 5 months and 4 years for the alleviation of intractable epilepsy, cerebral glucose utilization was studied serially with positron emission tomography. Three to 7 months after hemispherectomy, glucose utilization in the caudate nuclei on the side of hemispherectomy had decreased to below preoperative values, presumably due to total deprivation of ipsilateral cortical input. One to 2.5 years after surgery, complete restoration of glucose metabolic activity to preoperative levels was seen in 2 patients and partial recovery was seen in 1 patient. These alterations of cerebral glucose utilization are believed to reflect microscopic anatomical reorganizational changes (e.g., collateral sprouting) that have been documented following similar lesions in several animal models. Our findings suggest that positron emission tomography may provide a sensitive measure of developmental brain plasticity in vivo.

Functional brain imaging with positron emission tomography (PET) has led to significant advances in the diagnosis and management of various forms of childhood epilepsy. Interictal PET in temporal lobe epilepsy typically shows decreased glucose utilization (hypometabolism) in one or both temporal lobes. Children with early-onset refractory extratemporal lobe epilepsy who do not manifest structural abnormalities on magnetic resonance imaging often show single or multiple cortical foci of hypometabolism indicating underlying microdysgenesis that corresponds to the area of epileptogenicity. The findings of focal cortical metabolic lesions and metabolic activation of subcortical structures (brain stem and lenticular nuclei) in patients with infantile spasms have allowed many infants with intractable spasms to be treated surgically with cortical resection, and have altered our concepts regarding the pathophysiology of these seizures. New observations in Lennox-Gastaut syndrome, Sturge-Weber syndrome, tuberous sclerosis, hemimegalencephaly, Landau-Kleffner syndrome, and other pediatric epilepsy syndromes have been documented with PET and have improved our understanding of these disorders. Recent PET studies of several neurotransmitter receptors in adult epileptic patients suggest that this approach holds great promise in the study of childhood epilepsy. The current guidelines indicating which patients with epilepsy should be referred for a PET study are outlined.

We have studied seven patients with Spielmeyer-Vogt disease (SV), aged 11-29 years, using PET and 2-deoxy-2[18F]fluoro-D-glucose. Five patients showed a distinctive age-related progression with decreased metabolic activity starting in the calcarine area and spreading rostrally to the entire cortex, leaving normal uptake only in the basal ganglia and brainstem of the oldest patients. Calcarine hypometabolism was mild in the youngest patient. All patients, including the youngest when the study was repeated 2 years later, had significantly decreased calcarine metabolic activity (P = 0.002). Two patients had PET patterns markedly different from the five others, with significantly decreased metabolic activity in most brain areas. Both patients may represent a new SV variant. An adult pathological control with congenital amaurosis showed normal cerebral metabolic activity in all areas. Two patients had older sisters, one now deceased, the other not available for study, who presented a rapid regression associated with epilepsy. Phenytoin and carbamazepine probably caused increased seizure activity and faster regression. The younger siblings treated with phenobarbital monotherapy had few seizures and maintained motor functions 5-8 years longer compared with their respective sisters. While the clinical course made obvious that some areas, such as the macula, are damaged before others, the progression from the calcarine area to the more anterior regions (but sparing the basal ganglia) provides unexpected insights into selective vulnerability of neurons that will allow a more precise way of monitoring individual patients.

To determine seizure propagation patterns, we analyzed ictal positron emission tomography (PET) studies of regional cerebral glucose utilization in 18 children (11 male and 7 female aged 2 weeks to 16 years) with epilepsy (excluding infantile spasms IS). Three major metabolic patterns were determined based on degree and type of subcortical involvement: Nine children had type I; asymmetric glucose metabolism of striatum and thalamus. Of these, the 7 oldest children showed unilateral cortical hypermetabolism (always including frontal cortex) and crossed cerebellar hypermetabolism. Two infants (aged < 1 year) had a similar ictal PET pattern but no cerebellar asymmetry, presumably owing to immaturity of corticopontocerebellar projections. Five children had type II, symmetric metabolic abnormalities of striatum and thalamus; this pattern was accompanied by hippocampal or insular cortex hypermetabolism, diffuse neocortical hypometabolism, and absence of any cerebellar abnormality. Four children had type III, hypermetabolism restricted to cerebral cortex. This classification can accommodate ictal PET and single photon emission computed tomography (SPECT) patterns described by other investigators. Future studies should be directed at the clinical relevance of this classification, particularly with regard to epilepsy surgery.