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Purpose: To identify the characteristic MR findings in extrapyramidal cerebral palsy., Method: Six patients who had suffered intrapartum asphyxia and who subsequently developed extrapyramidal cerebral palsy were identified. Asphyxia was evidenced by severe neonatal systemic acidosis as documented by a venous cord pH of less than 7.0 whenever available, or acidosis in subsequent arterial blood gas samples, and clinical signs of an acute hypoxic-ischemic encephalopathy during the neonatal period. In addition, 1- and 5-minute Apgar scores were 3 or less, and there had been need for intubation or vigorous resuscitation in the delivery room. There were three boys and three girls, all born at term, with birth weight appropriate for gestational age, and without a history of bilirubin levels above 15 mg/dL. MR imaging at 1.5 T was performed between 1 and 19 years of age., Results: In all subjects focal high signal abnormality was demonstrated in the posterior putamen and the anterior or posterior thalamus. There were no other findings in most cases., Conclusion: MR demonstrated lesions in the putamen and thalamus in all of our six patients with severe extrapyramidal cerebral palsy who had suffered intrapartum asphyxia.

A major challenge in genetics is identifying the basis of human heritable disease. We describe an "exon scanning" technique which surveys exons in genomic DNA for sequence alterations. By hybridizing genomic DNA to RNA probes derived from cDNAs, we can use RNase A to survey entire coding regions, comprising exons spread across extensive regions of genomic DNA, for mutations associated with genetic disease. Exon scanning of the beta-globin locus in the DNA of patients with 12 different hemoglobinopathies detected all of the culpable single base substitutions and deletions, but not single base insertions. Our analysis also revealed unsuspected polymorphisms and corrected a diagnosis originally based on hemoglobin electrophoresis. Exon scanning of the ornithine aminotransferase gene in a gyrate atrophy patient detected and localized a mutation in the sixth exon. Subsequent PCR amplification and sequencing characterized this as a missense mutation (proline----glutamine). Exon scanning of genomic DNA for sequence alterations, in combination with PCR amplification and sequencing, should be a generally useful strategy for evaluating suspect genes in disorders of unknown etiology, as well as for clinical diagnosis.

Culture characteristics in a variety of media were determined in 18 skin fibroblast cultures from 8 subjects with Huntington's disease (HD) and 20 cultures from 10 control subjects. Skin fibroblasts from HD subjects consistently and reproducibly demonstrated maximal cell densities that were higher than control values. There was no significant difference in growth rates. The relationship of this phenomenon to the HD gene is unknown, as are its specificity and time of appearance in the course of the illness.

Kinky hair disease, first described in 1962, is a sex-linked disorder, with its gene located on the long arm of the X chromosome close to the centromere. The condition is marked by intellectural deterioration, seizures, and poorly pigmented, friable hair. Bony changes, resembling scurvy, tortuosities of the cerebral and systemic vasculature, and diverticuli of the bladder are also seen. Biochemically, the most diagnostic alteration is a marked reduction in blood copper and ceruloplasmin levels. The mechanism for the low serum copper has not been defined. Even though parental copper administration will correct the biochemical abnormalities, such treatment will not arrest cerebral deterioration.

The Monitoring System for Adverse Events Following Immunization of the Centers for Disease Control collects data on events temporally related to immunization. Occasionally, reports are received of neurologic disturbances temporally related to receipt of vaccine. Most of these disturbances are events that regularly occur in the absence of immunization. It is then difficult to determine whether the relationship between the immunization and illness is causal or coincidental. We developed a method to assess causation of serious neurologic events by probability theory. By combining epidemiologic information on disease incidence with specific elements of the patient history, an estimate of the odds of vaccine causation can be derived, based on rational assumptions rather than observer bias. The result is not a diagnosis but an estimate of probability.

Cerebral blood flow (CBF) and carbohydrate metabolism were studied in 5 normal children and 25 children, aged 40 months or less, with varying degrees of protein-calorie malnutrition (PCM). CBF in normal children and those suffering from grade I PCM was 90.3 +/- 5.7 ml/100 g/min, a value comparable with that obtained by other investigators, but the proportion of glucose taken up by the brain which combined with oxygen, the oxygen/glucose index (OGI), was 65.8%, indicating significant conversion of glucose into lactic acid. Cerebral lactic acid production was 45.3 micronM/100 g/min, and the respiratory quotient (R.Q.) was 1.00. With increasing severity of PCM, there was increased glucose utilization and a progressive reduction in the OGI. In grade IV PCM, CBF was 68.7 +/- 5.4ml/100g/min, and the OGI was 34.7%. Cerebral lactic acid production was 27.4 micronM/100 g/min, and the R.Q. rose to 1.52. These findings suggest that in severe human PCM the proportion of glucose undergoing aerobic oxidation is reduced, and that in addition to being converted to lactic acid, a significant proportion of glucose is transformed by the brain into long chain fatty acids.

When skin fibroblast cultures derived from subjects with Huntington's disease (HD) were grown in medium supplemented with lipid-deficient serum (LDS), growth rates were less than those of control cultures. The mean percentage increase in generation times for nine control cultures incurred by using LDS rather than fetal calf serum (FCS) was 8.0%. Four cultures from 2 patients with HD failed to grow in LDS but grew well in medium supplemented with FCS. In nine other cultures derived from 7 patients with HD the mean percentage increase in generation time incurred by using LDS was 88.1%. Returning cultures to FCS or adding a mixture of linoleic and linolenic acids restored the growth rate of HD cultures to normal.