Prevalence of Sigmoid Sinus Dehiscence and Diverticulum among Adults with Skull Base Cephaloceles.

BACKGROUND AND PURPOSE: Cephaloceles are relatively rare conditions caused by a congenital and/or acquired skull defect. The incidence of associated venous brain anomalies with regard to cephaloceles remains to be fully elucidated. Accordingly, we sought to assess the prevalence of sigmoid sinus dehiscence and diverticula in patients with spontaneous skull base cephaloceles. MATERIALS AND METHODS: Our institutional data base was retrospectively queried from 2005 to 2018. Patients in whom spontaneous skull base cephaloceles were identified were ultimately included in the study cohort. These patients subsequently had their sigmoid sinuses re-evaluated with focused attention on the possible presence of dehiscence and/or diverticula. RESULTS: We identified 56 patients: 12 men and 44 women. After re-evaluation of the sigmoid sinuses, evidence of dehiscence and/or diverticula was noted in 21 patients. The right sigmoid sinus was involved in 11 patients, and the left sigmoid sinus was involved in 7 patients, including 3 cases of diverticulum. In 3 patients, evidence of bilateral sigmoid sinus dehiscence and diverticula was noted. Female sex was associated with sigmoid sinus dehiscence and diverticula by univariate analysis (P = .019). By linear regression, cephalocele volume was negatively associated with sigmoid sinus dehiscence and diverticula (coefficient, -2266, P value < .007, adjusted R 2 = 0.1077). By univariate logistic regression using average cephalocele volume as a cutoff, we demonstrate a statistically significant finding of lower volumes being associated with sigmoid sinus dehiscence and diverticula with an odds ratio of 3.58 (P = .05). CONCLUSIONS: The prevalence of sigmoid sinus dehiscence and diverticula in patients with cephalocele is high. Female sex is associated with sigmoid sinus dehiscence and diverticula. The cephalocele volume appears to be inversely proportional to sigmoid sinus dehiscence and diverticula.

Free tryptophan as an indicator of brain serotonin synthesis in infants.

This study confirms observations made in a former study of plasma of preterm and term newborn infants with intrauterine malnutrition during the first month of life and extends to the lactational period. The free fraction of L-tryptophan, the precursor amino acid of brain serotonin synthesis, is significantly elevated up to 3 months of age. According to previous results, which demonstrated that L-tryptophan and serotonin synthesis are increased in the brain of gestationally malnourished rats, the present data in humans malnourished early in life strongly suggest that the elevation of the free fraction of L-tryptophan in plasma provides an increased amount of the precursor molecule to pass across the blood-brain barrier and activates the synthesis of brain serotonin. Because serotonin has been found to have a possible neurotrophic role in the fetal brain, any alteration of its metabolism in this period could reflect as a permanent change in brain neurogenesis. The data suggest that the free fraction of plasma L-tryptophan may be an indirect marker of changes in brain serotonin synthesis in these patients. Additional data on the functional relevance of the brain serotonergic system in humans are required to support this hypothesis.

Nutritional recovery does not reverse the activation of brain serotonin synthesis in the ontogenetically malnourished rat.

In the present work we confirm that gestational malnutrition effects body and brain composition and results in an activation of the synthesis of the brain neurotransmitter 5-hydroxytryptamine. These results also demonstrate more activity of the rate-limiting enzyme tryptophan hydroxylase in the malnourished fetal and postnatal brain. However, the activity of this enzyme remains increased in the brain of nutritionally recovered animals accompanied by an increase in the synthesis of 5-hydroxytryptamine. We therefore suggest that, in the nutritionally recovered animal, the mechanism of activation of this biosynthetic path in the brain may be not dependent on the increased availability of free L-tryptophan observed in malnourished animals, but might be due to a specific change in the enzyme complex itself. This hypothesis is supported by the fact that plasma free and brain L-tryptophan return to normal in the recovered animal.

Early nutritional changes modify the kinetics and phosphorylation capacity of tryptophan-5-hydroxylase.

Gestational malnutrition induces an acceleration of the serotonin biosynthetic pathway in the developing brain with an increase in brain L-tryptophan (L-Trp), tryptophan-5-hydroxylase (TrpOH) activity and serotonin content. In the present work we report results on the possible mechanism of TrpOH activation. Kinetic experiments were done with different L-Trp concentrations in the rat brain at different ages. Also various phosphorylating conditions of the enzyme were tested in order to compare its activation in developmentally malnourished and normal brains. The results showed lower Km values and no changes in the Vmax in the malnourished as compared to controls. Interestingly, in the malnourished group, TrpOH showed an increased activity under the phosphorylating conditions employed. We propose that in the activation of brain TrpOH by developmental malnutrition, not only is an elevation of L-Trp involved, but also a change in the enzyme itself reflected in a higher affinity for L-Trp and in a greater response to phosphorylation. This allows us to propose the possibility that early chronic malnutrition induces structural changes in the enzymatic molecule.

Newborn humans and rats malnourished in utero: free plasma L-tryptophan, neutral amino acids and brain serotonin synthesis.

In the present study we report results concerning 5-hydroxytryptamine (5-HT) metabolism in two groups of small for date (SFD) human babies (gestational age 36 and 3 weeks), who suffered intrauterine nutritional restriction. A complementary study in the brain of rat fetuses with two types of intrauterine deprivation, in which brain L-tryptophan (L-Trp), tryptophan-5-hydroxylase (T5-H) activity and 5-HT content were determined on days 17, 19 and 21 of gestation. The same parameters studied prenatally were followed in both species during the immediate postnatal period. In the SFD babies the results were: (a) the free fraction of plasma L-Trp was significantly elevated; (b) plasma neutral amino acids were not substantially modified; (c) the bound fraction of L-Trp and plasma proteins were significantly low, as compared to controls. In the fetal brain of intrauterine malnourished rats, L-Trp, activity of T5-H and 5-HT content, were significantly elevated, since day 17, as related to normal littermates. These alterations in 5-HT metabolism persisted during the early postnatal period in both species. Elevation of the free fraction of plasma L-Trp in early malnourished SFD human babies suggest an increased transport of this amino acid to the brain with a possible enhancement of serotonin synthesis, during a critical period of brain differentiation.

Perinatal brain serotonin metabolism in rats malnourished in utero.

The fetal brain serotonin metabolism has been studied in two types of gestationally malnourished rats: protein-calorie and after ligation of one branch of the uterine artery. The results showed an elevation of L-tryptophan and serotonin content and an enhancement of tryptophan-5-hydroxylase activity in the malnourished fetal brain, continuing up to day 10 of postnatal life. The possible implications of these early changes of the serotoninergic system in brain differentiation and a lasting change in tryptophan-5-hydroxylase kinetics are proposed for further study.

Brain serotonin synthesis and Na+,K+-ATPase activity are increased postnatally after prenatal administration of L-tryptophan.

The effect of prenatal L-tryptophan supplementation on the serotonin (5-HT) synthesis and the activity of Na+,K+-ATPase in the cerebral cortex was studied during postnatal development, from birth up to day 30. A parallel and significant elevation of the serotonin content and the activity of tryptophan-5-hydroxylase was observed in the brain of infant rats born to mothers treated with L-tryptophan, as related to non-treated controls. The activity of Na+,K+-ATPase was also significantly elevated at the different ages studied throughout the developmental period, as related to controls. These results suggest an important role of L-tryptophan in the early regulation of the serotonin-synthesizing machinery, which lasts postnatally. Elevation of ATPase activity seems to be associated to the elevation in the activity of the 5-HT system.

Existence of [(3)H]serotonin binding sites in the rat spinal cord: A developmental study.

[(3)H]5-HT specific binding sites have been characterized in the rat spinal cord. Experimental conditions allowed us to study a single class of sites possibly related to the postsynaptic receptor for 5-HT. Binding constants (KD and Bmax) are described for adult and developing animals. No substantial changes in affinity were observed but the number of receptors increased from birth up to day 20 postnatally, stabilizing thereafter. The developmental pattern of a presynaptic marker, tryptophan-5-hydroxylase, was similar to that of binding sites.