Thyroid function in children with epilepsy treated with sodium valproate monotherapy: a prospective study.

OBJECTIVE: Studies on the effects of sodium valproate (VPA) on thyroid hormone balance in patients with epilepsy are conflicting. The aim of this study was to prospectively evaluate the changes in thyroid profile in children with epilepsy treated with VPA monotherapy. METHODS: Serum thyroxine, free thyroxine, triiodothyronine, and thyrotropin (TSH) levels were evaluated in 30 children with epilepsy, before and at 6, 12, and 24 months of VPA monotherapy. RESULTS: All children had normal thyroid function before the initiation of VPA treatment. Serum VPA concentrations remained within the therapeutic range (50-100 mg/L) during the period of study. Thyroxine and free thyroxine levels were significantly decreased, whereas TSH levels were significantly increased at 6, 12, and 24 months of VPA therapy. Triiodothyronine levels were significantly decreased only at 24 months of therapy. Thirteen children (43.3%) at 6 months, 14 children (46.6%) at 12 months, and 15 children (50%) at 24 months of treatment had TSH values greater than 5 mIU/mL. Normal serum TSH levels were restored in all 8 children examined at 3 months after withdrawal of medication. CONCLUSIONS: Valproate monotherapy may cause significant alteration in thyroid profile in children with epilepsy, occurring early in the course of treatment and persisting as long as VPA is initiated. Therefore, it may be useful to measure serum thyroid hormone concentrations routinely in children with epilepsy taking VPA. Further prospective studies are required to determine the mechanisms and risk factors for development of thyroid disturbance in children treated with VPA monotherapy.

Acute acalculous cholecystitis in children with Epstein-Barr virus infection: a role for Gilbert's syndrome?

Acute acalculous cholecystitis (AAC) in association with acute Epstein-Barr virus (EBV) infection has rarely been described in childhood. In the literature, there are only four reported pediatric cases of AAC associated with isolated primary EBV infection. We present two cases (one new, one retrospectively reviewed) of children with Gilbert's syndrome (GS) who presented with AAC during the course of primary EBV infection. Antibiotics were not used and AAC subsided gradually as the infection regressed. The co-occurrence of GS might have played a contributory role in the pathogenesis of AAC during acute EBV infection.

Transient decrease in serum albumin concentrations in epileptic children treated with sodium valproate monotherapy.

OBJECTIVE: Hypoalbuminemia has been reported in patients with severe disability and epilepsy and in patients with epilepsy treated with short-term sodium valproate (VPA) therapy; however, serum albumin concentrations have not previously been determined in otherwise healthy patients with epilepsy and receiving long-term VPA monotherapy. METHODS: Serum albumin concentrations were determined in 26 ambulatory children with epilepsy before and at 6, 12, and 24 months of VPA monotherapy. Serum total protein concentrations and serum concentrations of other biochemical markers of liver and renal function such as alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, and creatinine concentration were also measured in the study participants before and at 6, 12, and 24 months of treatment. RESULTS: Serum albumin concentrations were reduced at 6 months of treatment (P = 0.007). Serum alanine aminotransferase concentrations were significantly increased at 6 (P = 0.034) and 12 months of treatment (P = 0.046), whereas serum aspartate aminotransferase concentrations were significantly increased at 6 (P = 0.002) and 12 months of treatment (P = 0.002). There were no significant correlations between serum albumin and the other parameters at 6 months of treatment. CONCLUSIONS: Ambulatory children who receive VPA monotherapy may have early but transient decrease in serum albumin concentrations. Further studies are needed to address this issue and to determine the possible clinical implications and the mechanisms involved in VPA-mediated decrease in serum albumin concentrations.

Thyroid dysfunction associated with increased low-density lipoprotein cholesterol in epileptic children treated with carbamazepine monotherapy: a causal relationship?

OBJECTIVE: Lipid abnormalities and thyroid dysfunction have been reported in patients treated with antiepileptic drugs. The aim of this study was to evaluate prospectively the association between thyroid and lipid profile in children treated with carbamazepine (CBZ) monotherapy. MATERIALS AND METHODS: Thyroid function was evaluated in 18 epileptic children, previously reported with CBZ-induced changes in serum lipid profile, before and at 6, 12 and 24 months of CBZ monotherapy. RESULTS: All children had normal thyroid function before the initiation of CBZ treatment. During CBZ therapy thyroid dysfunction, with increased thyrotropin (TSH) and decreased thyroxine (T4), free thyroxine (FT4) and triiodothyronine (T3) was found, while, significant association was revealed between serum low-density lipoprotein cholesterol (LDL-C) and TSH levels at 6 (r=0.469; p=0.043) and 12 (r=0.730; p=0.001) months of treatment. CONCLUSION: Lipid abnormalities may be associated with thyroid hormone disturbance in children treated with CBZ monotherapy. Since thyroid dysfunction and hypercholesterolemia are both associated with a higher atherosclerotic risk special attention and further studies are needed in epileptic patients treated with CBZ monotherapy.

Acute acalculous cholecystitis as the initial presentation of primary Epstein-Barr virus infection.

The case of a 13-year-old girl with primary Epstein-Barr virus (EBV) infection and concomitant cholestatic hepatitis, which initially presented as acute acalculous cholecystitis (AAC), is described. The diagnosis of AAC was documented by clinical and ultrasonographic criteria, whereas acute EBV infection was confirmed serologically. AAC may develop during the course of acute EBV infection, especially in patients with cholestatic hepatitis.

Effect of sodium valproate monotherapy on serum uric acid concentrations in ambulatory epileptic children: a prospective long-term study.

PURPOSE: Hyperuricemia has been shown to be related to cardiovascular morbidity and mortality. There is controversial data about the effect of sodium valproate (VPA) monotherapy on serum uric acid concentrations. The purpose of this study was to investigate by a long-term, prospective method, whether treatment with VPA monotherapy may alter serum uric acid concentrations and liver function tests in ambulatory epileptic children. MATERIAL AND METHODS: Serum uric acid concentrations were determined in 28 ambulatory epileptic children before and at 6, 12 and 24 months of VPA monotherapy. Serum concentrations of biochemical markers of liver and renal function, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyltransferase (gamma-GT) and creatinine (Cr) were also measured before and at 6, 12 and 24 months of VPA monotherapy. Serum VPA concentrations remained within the therapeutic range (50-100 mg/L) during the period of study. RESULTS: No statistically significant changes in serum uric acid concentrations were found at 6, 12 or 24 months of treatment. Serum ALT concentrations were significantly increased at 6 and 12 months of treatment, AST concentrations at 6 and 12 months of treatment and LDH concentrations at 12 months of treatment. CONCLUSIONS: VPA monotherapy does not have a significant effect on serum uric acid concentrations in ambulatory epileptic children. Further studies are needed to definitively address whether it would be useful for physicians to routinely check for elevated serum uric acid levels in children treated with VPA.

Homozygous MTHFR C677T gene mutation and recurrent stroke in an infant.

The role of homozygosity for the C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene as an independent risk factor for primary and recurrent stroke has been questioned, although recent data appear to be supportive. However, the association of homozygous C677T MTHFR mutation with silent brain infarctions in infancy has not been reported. The authors describe an 11-month-old male who had suffered a silent brain infarction followed by a symptomatic arterial stroke. The evaluation revealed mildly elevated homocysteine levels secondary to homozygous C677T alleles for MTHFR and iron deficiency anemia. An extensive evaluation for other causes of infarction was negative. We suggest that the mother's homozygous MTHFR status played a role in the early onset of stroke and that iron deficiency anemia may have contributed to the recurrence. The patient was treated with anticoagulation therapy, folic acid, and iron supplementation and has not had a recurrent event during 3 years of follow-up. This case provides further evidence that homozygous MTHFR mutation is a predisposing factor for early and recurrent pediatric stroke, including silent infarcts, especially in the presence of other risk factors.

Early and persistent increase in serum lipoprotein (a) concentrations in epileptic children treated with carbamazepine and sodium valproate monotherapy.

PURPOSE: The aim of this study was to investigate by a prospective, self-controlled method, whether treatment with carbamazepine (CBZ) and sodium valproate (VPA) monotherapy may alter serum lipoprotein (a) [Lp(a)] concentrations in epileptic children. METHODS: Serum Lp(a) concentrations have been determined in 18 epileptic children before and at 6, 12 and 24 months of treatment with CBZ monotherapy and in 30 epileptic children before and at 6, 12 and 24 months of treatment with VPA monotherapy. Serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoproteins A-I and B concentrations and serum concentrations of biochemical markers of liver and renal function were also measured in the study participants. RESULTS: Serum Lp(a) concentrations were significantly increased at 6, 12 and 24 months of CBZ and VPA monotherapy. There were no significant correlations between serum Lp(a) and serum lipids, lipoproteins, apolipoproteins, concentrations of biochemical markers of liver and renal function or antiepileptic-drugs concentrations. CONCLUSIONS: Children who receive CBZ or VPA monotherapy may have significant and persistent increase in serum lipoprotein (a) concentrations, occuring early in the course of therapy. It may be useful to measure serum Lp(a) concentrations routinely in epileptic children taking these antiepileptic drugs, especially in those that are already at higher atherosclerotic risk.

Serum total amylase, pancreatic amylase and lipase activities in epileptic children treated with sodium valproate monotherapy.

To investigate by a prospective, self-controlled method, whether early treatment with sodium valproate (VPA) monotherapy has some effect on serum total amylase and particularly on its pancreatic isoenzyme and lipase activities in epileptic children. Serum total amylase, pancreatic amylase and lipase activities have been evaluated in 23 epileptic children, before and at 6 and 12 months of VPA monotherapy. All children remained without clinical symptoms of pancreatitis during the period of study. Serum pancreatic amylase activities were significantly decreased at 6 and 12 months of treatment with VPA, whereas serum total amylase and lipase activities did not show any significant changes at 6 or 12 months of treatment. Non-pancreatic isoenzyme activities of amylase were significantly higher at 6 and 12 months of treatment. Three patients (13%) had slightly elevated serum total amylase levels at 6 and 12 months of treatment. There was no significant correlation of serum pancreatic amylase levels or non-pancreatic isoenzyme levels of amylase with serum VPA levels at 6 and 12 months of treatment. Non-pancreatic amylase activities, probably derived from salivary glands, may be increased in children treated with VPA monotherapy. Measurement of serum pancreatic amylase and/or serum lipase activities is indicated in patients with increased serum total amylase levels but without clinical symptoms of pancreatitis and, furthermore, in patients with symptoms suggesting dysfunction of pancreas, in order to avoid unnecessary discontinuing of VPA.

Classic transient erythroblastopenia of childhood with human parvovirus B19 genome detection in the blood and bone marrow.

The etiology of transient erythroblastopenia of childhood (TEC) remains unknown, although an association with viral infections has been proposed. The authors describe a 3.5-year-old girl with classic TEC concomitantly with human parvovirus B19 (HPV) infection. The infection was evident by detection of HPV genome in the blood and the bone marrow by polymerase chain reaction. Viral genome was no longer detected when the TEC resolved clinically. The patient was immunocompetent and the anemia has not recurred. To the authors' knowledge, this is one of the few documented cases of classic TEC attributable to HPV infection.