No abstract

The aim of this study was to determine whether activation of central type II glucocorticoid receptors can blunt autonomic nervous system counterregulatory responses to subsequent hypoglycemia. Sixty conscious unrestrained Sprague-Dawley rats were studied during 2-day experiments. Day 1 consisted of either two episodes of clamped 2-h hyperinsulinemic (30 pmol x kg(-1) x min(-1)) hypoglycemia (2.8 +/- 0.1 mM; n = 12), hyperinsulinemic euglycemia (6.2 +/- 0.1 mM; n = 12), hyperinsulinemic euglycemia plus simultaneous lateral cerebroventricular infusion of saline (24 microl/h; n = 8), or hyperinsulinemic euglycemia plus either lateral cerebral ventricular infusion (n = 8; LV-DEX group), fourth cerebral ventricular (n = 10; 4V-DEX group), or peripheral (n = 10; P-DEX group) infusion of dexamethasone (5 microg/h), a specific type II glucocorticoid receptor analog. For all groups, day 2 consisted of a 2-h hyperinsulinemic (30 pmol x kg(-1) x min(-1)) or hypoglycemic (2.9 +/- 0.2 mM) clamp. The hypoglycemic group had blunted epinephrine, glucagon, and endogenous glucose production in response to subsequent hypoglycemia. Consequently, the glucose infusion rate to maintain the glucose levels was significantly greater in this group vs. all other groups. The LV-DEX group did not have blunted counterregulatory responses to subsequent hypoglycemia, but the P-DEX and 4V-DEX groups had significantly lower epinephrine and norepinephrine responses to hypoglycemia compared with all other groups. In summary, peripheral and fourth cerebral ventricular but not lateral cerebral ventricular infusion of dexamethasone led to significant blunting of autonomic counterregulatory responses to subsequent hypoglycemia. These data suggest that prior activation of type II glucocorticoid receptors within the hindbrain plays a major role in blunting autonomic nervous system counterregulatory responses to subsequent hypoglycemia in the conscious rat.

The presence of ring-enhancing lesions in brain magnetic resonance images (MRIs) often raises the concern of an infectious etiology, although this radiographic finding is also seen in patients with multiple sclerosis. Multiple ring-enhancing lesions have been reported in adult patients diagnosed with multiple sclerosis but have not yet been reported in childhood multiple sclerosis. We report here a 14-year-old girl with recurrent neurologic symptoms. Her initial brain MRI showed multiple ring-enhancing lesions involving numerous white-matter fiber tracts. An extensive investigation for infectious etiologies was unrevealing. Studies of cerebrospinal fluid showed an elevated myelin basic protein and the presence of an oligoclonal band not seen in the serum. The results of electrophysiologic studies suggested a demyelinating process. The patient responded rapidly to high-dose corticosteroid treatment. However, she suffered a clinical relapse 3 months later, presenting with dysesthesia and weakness of the right arm. Repeat MRI showed multiple new active lesions. This case report illustrates that multiple ring-enhancing lesions in the brain MRI can be seen in children with multiple sclerosis and that multiple sclerosis should be considered as part of the differential diagnosis when encountering a pediatric patient with similar radiographic findings.