Manuel Castro-Gago

Effects of long‐term treatment with antiepileptic drugs on serum lipid levels in children with epilepsy

Article abstract—We determined serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TGs) in 125 healthy children and in 119 children with epilepsy who had been receiving carbamazepine (58 children), pheno-barbital (22 children), or valproic acid (39 children) for 7 months to 10.5 years (mean, 5.8 years). None of the variables considered was significantly correlated with time elapsed since start of treatment or with drug concentration in serum. In the groups receiving carbamazepine or phenobarbital, mean TC, HDL-C, and LDL-C levels were higher than in the control group, the differences being statistically significant for all except LDL-C in the phenobarbital group. In neither group did mean TC/HDL-C ratio or mean LDL-C/HDL-C ratio differ significantly from the corresponding control-group mean. In the group receiving valproic acid, mean TC level, mean LDL-C level, mean TC/HDL-C ratio, and mean LDL-C/HDL-C ratio were significantly lower than in the control group. In none of the treated groups did mean VLDL-C or TG level differ significantly from the corresponding control-group mean. Our results suggest, in contrast to previous reports, that the effects on the serum lipid profile of long-term treatment with hepatic-enzyme—inducing antiepileptic drugs (such as carbamazepine and phenobarbital) are probably not beneficial as regards risk of atherosclerosis-related disease. Our results additionally suggest a need for careful monitoring of serum cholesterol levels in children with epilepsy receiving carbamazepine or phenobarbital.

The effects on lipid and apolipoprotein serum levels of long-term carbamazepine, valproic acid and phenobarbital therapy in children with epilepsy

The aim of the present study was to assess the effect of long-term carbamazepine (CBZ), valproic acid (VPA) and phenobarbital (PB) treatment on serum lipids and apolipoproteins in epileptic children. Serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) and triglycerides (TGs) were measured and the LDL-C/HDL-C and TC/HDL-C ratios were calculated in 320 children and adolescents (129 receiving CBZ, 127 receiving VPA and 64 receiving PB) suffering from various types of epilepsy. Additionally, in a subgroup of 181 children (68 CBZ; 78 VPA; 35 PB) apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), HDL2-C and HDL3-C were measured and apoA-I/apoB and HDL2-C/HDL3-C ratios were calculated. Results of the measurements were compared with those of 169 age-and sex-matched healthy controls. None of the variables considered was significantly correlated with time elapsed since start of treatment or with drug concentration in serum. TC and LDL-C serum levels were high in children receiving CBZ or PB and low in those treated with VPA. Serum LDL-C level exceeded 130 mg/dl in 27.9% of CBZ-group, 31.8% of the subjects receiving PB, but only in 7% of those receiving VPA and in 11.8% of control group subjects. CBZ-treated children also showed high HDL-C and HDL3-C values. In the group receiving VPA, HDL2-C, HDL2-C/HDL3-C ratio and apo B were significantly lower than in the control group. Mean apoA-I levels were low in all treated groups: by contrast, in neither group did TGs, VLDL-C levels and TC/HDL-C or LDL-C/HDL-C ratios differ significantly from the corresponding control group. Our results suggest that the effects of long-term AED therapy on lipid profile and, particularly, on apolipoprotein serum levels increase risk of atherosclerosis-related disease. Moreover, these results confirm our previously reported increased risk in CBZ and PB-treated patients.

Clinical heterogeneity associated with mitochondrial DNA depletion in muscle.

We studied 10 patients with a variable degree of mtDNA depletion in muscle. Seven patients showed a clear-cut myopathic pattern, while the three remaining had brain involvement. There was no relationship between age at onset and relative mtDNA copy number in muscle, but we found an apparent correlation between clinical severity and degree of muscle mtDNA depletion. Muscle morphology showed that mtDNA depletion was associated with mitochondrial proliferation and cytochrome c oxidase negative fibers. Biochemical studies revealed single or combined defects of mtDNA-dependent respiratory chain complexes. Our data indicate that patients with mtDNA depletion may have a more variable age at onset and clinical evolution and wider phenotype than previously thought. The diagnosis of this condition, so far regarded as rare, may have been overlooked to some extent.

SERUM CARNITINE LEVELS IN EPILEPTIC CHILDREN BEFORE AND DURING TREATMENT WITH VALPROIC ACID, CARBAMAZEPINE, AND PHENOBARBITAL

Serum levels of free, acyl, and total carnitine were determined in 32 patients with seizures, before and after 3, 6, and 12 months of treatment with valproic acid (17 patients), carbamazepine (10 patients), or phenobarbital (5 patients). In all three treated groups, both free and total carnitine levels showed a significant decline with respect to pretreatment levels. This decline was most marked and most consistent in patients treated with valproic acid. In 35% of the patients in this group, carnitine deficiency (ie, total camitine < 30 μmol/L) was observed by month 12. In none of the three groups were serum carnitine levels significantly correlated with the serum concentration of the drug. These findings suggest a need to monitor serum carnitine levels in children treated with any of these drugs. (J Child Neurol 1998;13:546-549).

Evolution of Serum Lipids and Lipoprotein (a) Levels in Epileptic Children Treated With Carbamazepine, Valproic Acid, and Phenobarbital

The concentration levels of serum lipids and lipoprotein (a) were measured in 20 children receiving carbamazepine, 25 children receiving valproic acid, and 5 children receiving phenobarbital at the following times: (1) during chronic treatment while eating a normal diet, (2) during chronic treatment while eating a low-fat diet (children treated with carbamazepine and phenobarbital with high levels of total choleserol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), and (3) 3 months after the end of treatment with antiepileptic drugs. Patients during chronic treatment and eating a normal diet revealed significant changes in lipids, but when we reevaluated the groups of children treated with carbamazepine and phenobarbital when they were eating a low-fat diet and reevaluated the three groups of children 3 months after the end of treatment, a complete return to normal of all parameters was observed. These data demonstrate that the changes induced by these drugs are transient, reversible, and influenced by a low-fat diet. (J Child Neurol 2006;21:48—53).

Neuron-specific enolase, nucleotides, nucleosides, purine bases, oxypurines and uric acid concentrations in cerebrospinal fluid of children with meningitis

To determine the effects of meningitis on cerebral energy metabolism, cerebrospinal fluid concentrations of adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine and urate were determined by high-performance liquid chromatography, and neuron-specific enolase by an enzyme immunoassay method, in 100 children with meningitis (45 bacterial, 46 viral and nine tuberculous), aged between 1 month and 13 years, and in 160 age-matched controls. Compared with controls, patients with bacterial meningitis showed high concentrations of hypoxanthine, xanthine and urate; patients with viral meningitis showed high concentrations of inosine, guanosine, xanthine, urate and neuron-specific enolase; and patients with tuberculous meningitis showed very high concentrations of inosine, xanthine and urate. Xanthine and urate concentrations were significantly higher in patients with tuberculous meningitis than in patients with viral or bacterial meningitis. These results suggest that in the acute stage of bacterial, viral and tuberculous meningitis, neuronal energy metabolism may be altered. The measurement of cerebrospinal xanthine and uric acid concentrations may be useful for the early diagnosis of a tuberculous origin.

Concentrations of nucleotides, nucleosides, purine bases and urate in cerebrospinal fluid of children with meningitis.

The release of agents mediating inflammation in meningitis may bring about neuronal hypoxia, under which circumstances ATP concentrations decrease and its degradation products increase and are released into the cerebrospinal fluid. In this study of alterations in neuronal energy metabolism in meningitis, AMP, IMP, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine and urate were determined by high performance liquid chromatography in the cerebrospinal fluid of 54 children aged between 1 month and 13 years suffering from meningitis (25 viral, 24 bacterial and 5 tuberculous cases) and 63 controls. Compared to the controls, patients with viral meningitis exhibited high concentrations of IMP, adenosine, guanosine, adenine, guanine and xanthine; patients with bacterial meningitis exhibited high concentrations of IMP, inosine, guanosine, adenosine, hypoxanthine, xanthine and urate; and patients with tuberculous meningitis exhibited high concentrations of AMP, guanosine, xanthine and uratc. Viral and bacterial cases did not differ significantly for any of the metabolites studied. AMP and urate concentrations were significantly higher in patients with tuberculous cases compared with viral or bacterial meningitis cases.

Hashimoto encephalopathy in a preschool girl.

Hashimoto encephalopathy is a steroid-responsive encephalopathy associated with elevated blood concentrations of antithyroid antibodies. The patients are usually euthyroid or mildly hypothyroid. The clinical picture is pleomorphic, presenting with variable symptoms ranging from behavioral and cognitive changes, myoclonus, seizures, pyramidal tract dysfunction, involuntary movements, and cerebellar signs to psychosis and coma, with relapsing and progressive course. The diagnosis is often overlooked at presentation but is crucial, given that this is a treatable disease. Described here, with a literature review, is the youngest patient reported to date with Hashimoto encephalopathy.

Convulsiones benignas durante gastroenteritis leve: a propósito de dos casos

Introduccion La presentacion de convulsiones benignas durante una gastroenteritis leve sin deshidratacion ni fiebre es una asociacion descrita con relativa frecuencia en Asia. Sin embargo, son escasas las referencias al tema fuera de dicho continente. Se trata de un proceso benigno que no implica un mayor riesgo de epilepsia ni de deterioro neuropsiquico. Casos clinicos Se describe el caso de dos ninas ingresadas en nuestro departamento en el ultimo ano por presentar convulsiones durante una gastroenteritis leve. En ambos casos las crisis fueron autolimitadas y la evolucion benigna. Conclusiones Esta entidad no se presenta exclusivamente en Asia y es probable que sea mas frecuente en nuestro medio de lo que se ha comunicado. Es importante tenerla presente ante un paciente con gastroenteritis y crisis convulsivas con el fin de evitar un tratamiento antiepileptico agresivo y/o prolongado.

Autosomal recessive hydrocephalus with aqueductal stenosis

We report the case histories of three sisters with congenital hydrocephalus associated with stenosis of the cerebral aqueduct. The parents were a young consanguineous couple. In two cases hydrocephalus was detected before birth by ultrasonography. We consider these three cases to be of the rare autosomal form of hereditary hydrocephalus.