Steroid-responsive encephalomyelitis in childhood

The syndrome of parainfectious encephalomyelitis evolves from an antecedent infection. Several etiologic agents have been associated with this complication, although the pathogenesis in each instance may prove to be more uniform. Considerable evidence suggests that the syndrome is mediated immunologically. The seven cases reported here were clinically similar, although the infectious etiologies were diverse. Leptospirosis antedated the neurologic syndrome in two cases, and a "viral" illness preceded the other five cases. The evolution of the syndrome was slowly progressive in each case, and six patients had prominent involvement of rhombencephalic structures. The progressive course was reversed rapidly with eventual full recovery in each instance after initiation of corticosteroid therapy. Our experience with these cases coupled with a review of the literature suggests that corticosteroid therapy should be considered in the subacute or chronic cases of parainfectious encephalomyelitis.     

Hartnup disease. Clinical, pathological, and biochemical observations

Hartnup disease is a rare genetic disorder of amino acid transport associated with variable and intermittent clinical abnormalities. A family is described in which three siblings had an intermittently progressive neurological disease and two of the affected siblings had the Hartnup-pattern aminoaciduria. Neuropathological examination of one case showed severe diffuse atrophy, generalized neuronal loss in the cortex, and Purkinje cell loss in the cerebellum. In vivo and in vitro studies of intestinal amino acid transport in the surviving sibling indicated a partial defect in the transport of several neutral amino acids (tryptophan, alanine, serine, and methionine) with normal transport of other neutral amino acids (threonine, phenylalanine, histidine, tyrosine, and isoleucine). Transport of glycine, proline, hydroxyproline, and the basic amino acids appeared normal.     

The effect of undernutrition on the development of myelin in the rat central nervous system

Newborn rats were segregated into litters of 6 and 22 pups. Undernourished groups were maintained for 21 and 53 days at which time a portion of each group was sacrificed and the remainder refed until 121 days. The amount of myelin isolated from the central nervous system was decreased in nutritionally deprived animals but there was little change in its chemical composition or intereference in the normal chemical maturation of the membrane. The only consistent change was a reduction in phosphatidyl ethanolamine plasmalogen. This deficit tended to be corrected by nutritional rehabilitation and was most complete in those animals refed ad lib. diets for the longest time periods prior to sacrifice. The relatively normal chemical composition of myelin obtained from undernourished animals differs from changes described in myelin membranes isolated from patients with destructive or degenerative diseases of the nervous system. This seems to be further evidence that the reduction in myelination in undernutrition is a result of decreased synthesis of the membrane.     

A follow-up study of Sydenham's chorea

Twenty-five patients convalescing from Sydenham's chorea were contrasted by clinical examination, electroencephalograms, and psychometric and psychologic tests to 15 siblings and 20 matched rheumatic fever controls. A group of 10 postchoreic patients who had two or more signs could be identified. Patients in this group had all the signs classified as moderate or severe, performed less well than other choreic subjects on the Bender gestalt test, and had a higher percentage of abnormal electroencephalograms but not a higher incidence of behavioral disorders. This subgroup could not be predicted from a review of neurologic history or from analysis of the acute episode of chorea. Our data would suggest that uncomplicated Sydenham's chorea is not necessarily a benign self-limited affliction of the central nervous system and that some patients are left with definite, albeit minimal, neurologic residua.     

The relationship of biochemical and morphological information in the central nervous system: The problem of sampling

The histology of the central nervous system (CNS) is complex, consisting of membranes derived from a number of cell types as well as specialized membranes associated with structural modifications of the neuron. The cell structure, and thus the membrane content, of the CNS varies with age and from area to area; in no instance is it possible to isolate a single cell type without special microdissection techniques. Neurological disease often involves specific areas of the CNS attacking one or all of the cellular elements in that region. In other instances, damage may be wide-spread, but at the histological level it may be restricted to a single cell type or even to a single membrane. The latter situation is particularly applicable to diseases that attack the myelin sheath. The biochemical investigation of changes in the lipid content of the brain resulting from neurological disease is hampered not only by the morphological complexity of nervous tissue, but by the tendency of destructive processes to be accompanied by proliferation of other cellular elements, both during the acute phase of disease and during the process of repair, which may mask significant abnormalities. Thus, in order to decide which changes in the structural lipids of the diseased brain are meaningful, a knowledge of the histopathology of the disorder is essential. When the morphological changes that accompany a neurological disorder are known, one may choose an appropriate tissue sample for study. Isolation of specific structural or functional subunits of the CNS, dissection of small groups of cells, isolation of single cells and separation of specific membranes are techniques available to sample nervous tissue. These are discussed, and their applicability to the biochemical study of specific neurological diseases is evaluated.     

A possible block in the intermediary metabolism of glucose into proteins and lipids in the brains of undernourished rats

[U-¹⁴C] Glucose or [1-¹⁴C] L-leucine was injected intraperitoneally into 28-day-old undernourished rats and control sibs who were killed 6 hr later. Brain proteins and lipids were extracted and the lipids fractionated by silicic acid column chromatography into cholesterol, glycolipids and phospholipids. The specific activity of labeled carbon derived from [U-¹⁴C] glucose in brain proteins was reduced by 25% in undernourished animals when compared to controls. A similar reduction was seen in the specific activity of brain lipids of undernourished animals: 14% for cholesterol, 21% for phospholipids and 35% for glycolipids. When [1-¹⁴C] l-leucine was used as a direct precursor of brain protein synthesis, the specific activity in the undernourished group was only 5% less than that found for the controls. This was not statistically significant. The results suggest that there may be a block in the intermediary metabolism of glucose in the brains of undernourished rats that reduces the availability of glucose carbon to the precursor pool used for protein and lipid synthesis.