No abstract

We analyzed lactate, pyruvate, and citric acid cycle intermediates in cerebrospinal fluid by high-performance liquid chromatography in Rett syndrome patients (n = 27; mean age, 5.7 +/- 3.4 years) and age-matched female controls (n = 12; mean age, 7.0 +/- 3.3 years). The lactate, pyruvate, alpha-ketoglutarate, and malate were significantly elevated in Rett syndrome compared to the controls. The lactate/pyruvate ratio was not different. On the other hand, cerebrospinal fluid citrate, cis-aconitate, succinate, fumarate, and oxaloacetate were not significantly different in Rett syndrome patients than in the controls. We also evaluated the correlation between these acids and clinical symptoms and signs, including clinical stage, seizures medications (anticonvulsants or naltrexone), developmental quotient, self-abuse, and hyperventilation or apnea or both. The concentrations of all these acids did not differ significantly with clinical stage. Lactate elevation significantly correlated with apnea. Lactate and pyruvate elevation significantly correlated with hyperventilation or with both breathing abnormalities. Our observations in this sample of patients with Rett syndrome led us to speculate that patients with the Rett syndrome may have defective carbohydrate metabolism. Elevated mitochondrial reduced nicotinamide-adenine dinucleotide-linked substrates suggest that reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase may be deficient in the brain in Rett syndrome patients.

No abstract

We performed a double-blind, placebo-controlled, crossover trial of sulfamethoxazole-trimethoprim (S-T) in 8 patients with Machado-Joseph disease (MJD), and measured the blood and cerebrospinal fluid levels of biopterins, biogenic amines or metabolites, and folate. The clinical results were as follows; mild improvements of hyperreflexia of knee jerks and of rigospasticity of the legs during S-T treatment period. In addition, S-T significantly reduced the times of 8 motor activities on the timed tests. The biochemical results showed that basal levels of all biopterins and homovanillic acid in the cerebrospinal fluid (CSF) were reduced to less than half the levels of those of controls with other neurological diseases. After S-T treatment, total and oxidized form of biopterins in the CSF increased significantly. Therefore, S-T may be effective to neurologic deficits through its mechanism of increasing the level of brain biopterins.

Partial trisomy 22 usually occurs through a 3: 1 meiotic segregation of the parental 1 lq;22q translocation carrier, which is the most common balanced translocation in man. Common neurologic findings are delayed psychomotor development and muscular hypotonia. There have been a few neuroradiologic and neuropathologic studies, which include ventricular dilatation, arrhinencephaly , and aplasia or hypoplasia of the cerebellar vermis, corpus callosum and pons. We here add one patient with partial trisomy 22 who had, in addition to the usual features, Dandy-Walker malformation, which, to our knowledge, is a previously undescribed feature.