Guido Morgese

Valproate-induced hyperammonemic encephalopathy

Valproic acid (VPA) is an effective anticonvulsant useful in many types of epilepsy and, although it is usually well tolerated, it has been associated with many neurological and systemic side effects. Among these, one of the most important is VPA-induced hyperammonemic encephalopathy (VHE): its typical signs are acute onset of impaired consciousness, focal neurologic symptoms, and increased seizure frequency. The pathogenesis of VHE is still unclear, but it has been suggested that hyperammonemia can produce encephalopathy via inhibition of glutamate uptake by astrocytes which may lead to potential neuronal injury and perhaps cerebral edema. Glutamine production is increased, whereas its release is inhibited in astrocytes exposed to ammonia. The elevated glutamine increases intracellular osmolarity, promoting an influx of water with resultant astrocytic swelling. This swelling could compromise astrocyte energy metabolism and result in cerebral edema with increased intracranial pressure. Moreover, VHE seems to be more frequently in patients with carnitine deficiency or with congenital urea cycle enzymatic defects.

Increased Bone Turnover in Prepubertal, Pubertal, and Postpubertal Patients Receiving Carbamazepine

Summary:  Purpose: To study the markers of bone turnover in epilepsy patients in the different stages of the pubertal growth before and after the beginning of carbamazepine (CBZ) monotherapy.

Vascular endothelial growth factor (VEGF) in children, adolescents and young adults with Type 1 diabetes mellitus: relation to glycaemic control and microvascular complications.

SUMMARY

Serum leptin changes in epileptic patients who gain weight after therapy with valproic acid

Article abstract Weight gain has been recognized as an adverse effect of valproic acid therapy, but there are are no data about serum leptin levels in patients receiving this drug. To evaluate if valproic acid treatment in epileptic patients in whom obesity develops modifies serum levels of insulin and leptin, 40 female patients with epilepsy were evaluated before therapy and after 1 year of therapy. At the end of follow-up, 15 patients were obese and showed higher serum leptin and insulin levels than patients who did not gain weight. As in other types of obesity, elevation of serum leptin concentrations is related to the increase in body mass index.

Insulin Resistance in Epileptic Girls Who Gain Weight After Therapy With Valproic Acid

Valproic acid is effective for treatment of many types of epilepsy, but its use in epileptic patients can be associated with an increase in body weight that could interfere with treatment compliance. The weight gain may result from different mechanisms, but the exact pathogenesis is still unknown. To evaluate insulin sensitivity in adolescents who gained weight during treatment with valproic acid, we studied 20 girls with different types of epilepsy: 15 patients had primary generalized seizures, including absence seizures (3 cases), and 5 patients had partial seizures. After 1 year of valproic acid treatment, the obese patients had serum insulin levels significantly higher than patients who did not gain weight (51.4 ± 25.3 versus 28.2 ± 12.9). Moreover, we observed that epileptic patients who gained weight were also insulin resistant in comparison with nonobese epileptic subjects. At the end of treatment, all patients showed normal levels of serum testosterone, androstenedione, dehydroepiandrosterone sulfate, follicle-stimulating hormone (FSH), and luteinizing hormone. We found no significant correlation between insulinemia and serum valproic acid concentrations in obese and nonobese patients treated with valproic acid. Our study demonstrates that basal hyperinsulinemia and insulin resistance can be present in patients who develop obesity during valproic acid treatment. Therefore, these obese patients could be exposed to the risks related to these metabolic abnormalities; if these data are confirmed in longer studies, these side effects may raise some concerns about the safety of valproic acid. (J Child Neurol 2002;17:265-268).

Increased bone turnover in epileptic patients treated with carbamazepine

Bone turnover has been investigated in 12 epileptic patients before and after treatment with carbamazepine and in 15 sex‐ and age‐matched control subjects. We found higher values of markers of bone formation (serum bone alkaline phosphatase, osteocalcin, and propeptides of types I and III procollagen) and of bone resorption (serum telopeptide of type I collagen and urine N‐telopeptides of type I collagen) in patients than in controls. Our study demonstrates that carbamazepine induces an increase of bone turnover. Ann Neurol 2000;47:385–388

Advanced glycation end products in children and adolescents with diabetes: relation to glycemic control and early microvascular complications.

OBJECTIVE The measurement of serum advanced glycation end products (S-AGEs) in children, adolescents, and young adults with diabetes to determine whether increased S-AGE levels may be associated with long-term glycemic control and early microvascular complications. STUDY DESIGN The study was performed in (1) 178 children and adolescents with type 1 diabetes mellitus (age range, 2 to 21 years, onset before the age of 12 years; duration longer than 2 years) without clinical and laboratory signs of microvascular complications, (2) 39 adolescents and young adults (age range, 16.1 to 28.8 years) with background or preproliferative retinopathy or persistent microalbuminuria, and (3) 98 healthy age- and sex-matched control subjects. RESULTS S-AGEs were significantly increased in preschool and prepubertal children with diabetes and were particularly elevated in pubertal subjects with diabetes compared with control subjects. S-AGEs were markedly increased in adolescents with early microvascular complications compared with both control subjects and diabetic patients without retinopathy or nephropathy. No correlation was found between S-AGEs and albumin excretion rate or blood pressure values. Glycated hemoglobulin values and S-AGEs were significantly correlated (r = 0.32; P <.01). In children with poorly controlled diabetes (HbA1 c >10%), long-term (2 years) improvement of glycemic control resulted in a significant reduction of S-AGE levels in preschool and prepubertal children, as well as in pubertal individuals. CONCLUSIONS S-AGE concentrations may be elevated even in preschool and prepubertal children with diabetes; this means that the risk of microvascular complications may be present at an early age. Improvement in glycemic control may be associated with a significant decrease in S-AGEs.

Analgesic effect of watching TV during venipuncture

Aims: To assess the analgesic effect of passive or active distraction during venipuncture in children. Methods: We studied 69 children aged 7–12 years undergoing venipuncture. The children were randomly divided into three groups: a control group (C) without any distraction procedure, a group (M) in which mothers performed active distraction, and a TV group (TV) in which passive distraction (a TV cartoon) was used. Both mothers and children scored pain after the procedure. Results: Main pain levels rated by the children were 23.04 (standard deviation (SD) 24.57), 17.39 (SD 21.36), and 8.91 (SD 8.65) for the C, M, and TV groups, respectively. Main pain levels rated by mothers were 21.30 (SD 19.9), 23.04 (SD 18.39), and 12.17 (SD 12.14) for the C, M, and TV groups, respectively. Scores assigned by mothers and children indicated that procedures performed during TV watching were less painful (p<0.05) than control or procedures performed during active distraction. Conclusion: TV watching was more effective than active distraction. This was due either to the emotional participation of the mothers in the active procedure or to the distracting power of television.

Serum copper, zinc, selenium, glutathione peroxidase and superoxide dismutase levels in epileptic children before and after 1 year of sodium valproate and carbamazepine therapy

To assess whether epileptic children have abnormal values of serum copper (Cu), zinc (Zn), selenium (Se), glutathione peroxidase (GSH-PX) and superoxide dismutase (CuZn-SOD), and to evaluate the effect of long-term therapy with sodium valproate (VPA) and carbamazepine (CBZ) on these parameters, we studied 36 epileptic patients before the beginning of therapy and after 1 year of therapy with VPA or CBZ. Before the beginning of therapy, there were no differences in levels of all parameters studied between controls and epileptics. After 1 year of therapy, patients treated with VPA and CBZ continued to show normal values. In conclusion our study demonstrates that epilepsy per se and treatment with VPA and CBZ do not affect levels of Cu, Zn, Se, GSH-PX and CuZn-SOD concentrations.

Childhood absence epilepsy: evolution and prognostic factors.

Summary:  Purpose: To evaluate how diagnostic criteria influence remission rates for patients with childhood absence epilepsy (CAE) and to assess clinical and EEG parameters as predictors of outcome.