Cerebellar astrocytoma manifesting as isolated, comitant esotropia in childhood.

PURPOSE: We encountered a 4 1/2-year-old girl with gradual onset of intermittent, comitant esotropia in the absence of diplopia and other neurologic findings. METHODS: Because of the patient's relatively advanced age and lack of response to hyperopic correction for accommodative esotropia, computed tomography of the head was performed. RESULTS: A large cerebellar astrocytoma was identified and successfully resected. After strabismus surgery, fusion was reestablished. CONCLUSIONS: The onset of comitant esotropia in an older child may indicate an underlying neurologic disorder.

Agents for the treatment of brain injury. 1. (Aryloxy)alkanoic acids.

Blunt and ischemic injuries of the brain have been shown to result in swelling that is predominantly limited to a single cell type, the astrocyte, within the complex cellular mosiac of cerebral gray matter. Evaluation of various diuretic (aryloxy)acetic acids in vitro using incubating cat brain slices and primary astrocyte cultures identified compounds with marked ability to inhibit brain tissue swelling. Some of the compounds significantly reduced the mortality and morbidity following acceleration/deceleration brain injury in anesthesized cats. A variety of (indanyloxy)alkanoic acids were synthesized which were analogous to the dually active (indanyloxy)acetic acids. Some of the 4-(indanyloxy)butanoic acids were found to be devoid of diuretic activity but to possess equal or greater activity than the dually active compounds in the in vitro and in vivo brain assays. Selected examples from both the (indanyloxy)acetic and 4-(indanyloxy)butanoic acid series showed marked chiral effects, with one enantiomer generally exhibiting a much greater activity than the other. A clinical study of severely head-injured patients treated with ethacrynic acid demonstrated a significantly improved outcome when compared to controls. These data suggest a clinical advantage for the nondiuretic (aryloxy)alkanoic acids which possess in vitro and in vivo activities in the cat brain assays that are comparable or superior to dually active compounds.

Adenosine-stimulated astroglial swelling in cat cerebral cortex in vivo with total inhibition by a non-diuretic acylaryloxyacid derivative.

The intact cerebral cortices of cats were exposed in vivo under normothermic conditions and superfused with isotonic artificial cerebrospinal fluid containing added 0.125 mM adenosine. This resulted in chloridecation-rich cerebrocortical swelling which was shown by electron microscopy to be associated with an expanded astroglial compartment. The addition of DCPIB, a non-diuretic acylaryloxyacid analogue of ethacrynic acid and an inhibitor of coupled chloride-cation transport in cerebral cortex in vitro, totally blocked astroglial swelling and the concomitant increases in tissue ion contents. These studies support our previous experiments on the mechanism of formation of astroglial swelling. The pathological consequences of astroglial swelling and the clinical applications of these findings are discussed.

Biology of glial swelling in experimental brain edema.

Most studies of clinically relevant cerebral edema emphasize the effect of added tissue fluid in white matter on gross distortion with transtentorial and subfalcine brain herniation. Our recent studies on altered tissue fluid compartmentation in cerebral gray matter suggest that significant microdistortion of relationships of capillaries to subserved tissue follows swelling of astroglia therein. Grave consequences to solute and gas exchange in focal regions may well be expected and are emphasized. The elucidation of the mechanisms of formation and inhibition of astroglial swelling by chemical agents, including chemically useful acylaryloxyacetic acid derivatives, are discussed. Furthermore, the effect of these agents in altering mortality and morbidity in a controlled, random study of animal head injury is presented.

Alterations in cat cerebrocortical capillary morphometrical parameters following K+-induced cerebrocortical swelling.

Histochemical, electron microscopic, and morphometrical techniques were employed in the determination of the effects attributed to K+-induced cerebrocortical swelling on cat cerebrocortical capillary diameter, length, surface area, volume, and minimal intercapillary distance. Bilaterally exposed and intact temporoparietal cerebral cortices of 4 conditioned adult cats were simultaneously superfused with isotonic, artificial CSF containing 3.5 mM K+ (control) and 54 mM K+ experimental), for 1h at 37 degrees C with monitoring of systemic vital function, hematocrit, arterial blood gases, and determination of cerebrocortical tissue water content. The mean values for cerebrocapillary diameter were 5% (P less than 0.05) greater in swollen tissues when compared with comparable mean values determined for controls. The values for minimal intercapillary distance determined from control and experimental animals plotted as relative frequency histograms represented two distinct populations (P less than 0.005). The significance of altered capillary morphometric parameters are discussed in relation to K+-induced cerebrocortical swelling.