Everolimus for the treatment of subependymal giant cell astrocytoma probably causing seizure aggravation in a child with tuberous sclerosis complex: a case report.

We are reporting on a 13.5-year-old girl with tuberous sclerosis complex (TSC) who was treated with everolimus because of giant cell astrocytoma and bilateral angiomyolipoma. She suffered from pharmacoresistant partial epilepsy with clusters of tonic and tonic-clonic seizures. Treatment with carbamazepine and sulthiame had led to a stable situation for more than 2.5 years. The dosage of everolimus had to be increased and refractory status epilepticus followed after 12 days. In the absence of any other possible cause, we believe that the status epilepticus was provoked by everolimus. So far, only a few cases of possible seizure aggravation by everolimus have been reported. The clinical relevance of possible negative effects in epileptic patients remains unclear. Similar observations should be documented and reported.

Importance of changes in gastric emptying for postprandial plasma glucose fluxes in healthy humans.

OBJECTIVE: Regulation of postprandial (pp) plasma glucose excursions is complex. Insulin and glucagon are thought to play the predominant role. Nevertheless, only 50% of the variation in pp plasma glucose excursions is explained by variations by the latter. Theoretically, gastric emptying (GE) should be another important factor. However, its impact on pp glucose homeostasis is unknown. RESEARCH DESIGN AND METHODS: We examined the consequences of pramlintide-induced delay in GE on pp glycemia and glucose fluxes, determined isotopically. GE was recorded by scintigraphy. Fourteen healthy subjects (8 men, 6 women; age 40 +/- 3 yr, body mass index 27.8 +/- 1.1 kg/m2) ate a mixed meal, and 30 microg of pramlintide (PRAM) or placebo (PBO) were injected subcutaneously. RESULTS: At 60 min, greater proportions of the initial gastric contents remained in the stomach (PBO vs. PRAM). Thereafter, GE slopes paralleled until 240 min. Fifty percent retention times were lower when PBO was given (P < 0.001). GE was greater from 240 min to the end of the PRAM experiments, so that only slightly greater proportions of the meal remained in the stomach at 330 min. Reductions of GE lowered pp glucose (7.5 +/- 0.3 vs. 6.0 +/- 0.2 mmol/l, P < 0.001), even though plasma insulin was lower with PRAM (164 +/- 13 vs. 138 +/- 13 pmol/ml, both P < 0.01). Reduction in total glucose appearance (P < 0.001) was due to reduced meal-derived glucose appearance (10.2 +/- 0.5 vs. 7.0 +/- 0.4 micromol.kg(-1).min(-1), P < 0.001). Endogenous glucose appearance was greater with PRAM (P < 0.001). Splanchnic glucose uptake was greater with PRAM (26.5 +/- 1.6 vs. 32.5 +/- 2.1%, P = 0.014). CONCLUSIONS: These data support the concept that GE is an important physiological regulator of pp glucose homeostasis in humans.

Somatic mosaicism and variable penetrance in doublecortin-associated migration disorders.

X-linked isolated lissencephaly sequence (XLIS) and subcortical band heterotopia (SBH) are allelic disorders caused by mutations in the doublecortin (DCX) gene. This genetic analysis of seven families revealed four novel mutations in the DCX gene. The authors detected a high rate of somatic mosaicism in male and female patients with variable penetrance of bilateral SBH including nonpenetrance in a heterozygous woman. In addition, the authors implemented prenatal diagnosis in a family with SBH/XLIS.