Konstantinos A. Voudris

Early effect of sodium valproate and carbamazepine monotherapy on homocysteine metabolism in children with epilepsy

Plasma total homocysteine (p-tHcy), serum folate (s-F), serum vitamin B-12 (s-B12) and plasma pyridoxal-5-phosphate (p-PLP) were measured in epileptic children before and after a 20-week period of sodium valproate (group A, n=32) and carbamazepine (group B, n=20) monotherapy. P-tHcy significantly increased in both groups, s-F and s-B12 significantly increased in group A, while s-F and p-PLP significantly decreased in group B. Our study showed an early effect of antiepileptic drug treatment on homocysteine metabolism.

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

PURPOSEnThe 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.nnnMETHODSnSerum 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.nnnRESULTSnSerum 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.nnnCONCLUSIONSnChildren 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.

Alkaline phosphatase and its isoenzyme activity for the evaluation of bone metabolism in children receiving anticonvulsant monotherapy.

This study aimed to investigate whether carbamazepine, sodium valproate or phenobarbital as monotherapy in ambulatory epileptic children with adequate sun exposure have some effect on their bone metabolism based on the determination of total serum alkaline phosphatase (AP) levels and its bone isoenzyme activity. Blood samples were obtained from 118 epileptic children (37 on carbamazepine, 47 on sodium valproate and 34 on phenobarbital) and from corresponding healthy controls matched for age, gender and anthropometric parameters. AP and its liver, bone and intestinal isoenzyme levels, other common biochemical markers of bone and liver metabolism and drug levels were measured in the study participants. Patients on carbamazepine or phenobarbital had significantly elevated AP levels accompanied by increased bone and liver isoenzyme activity compared to controls. An increase of bone AP isoenzyme values, correlated with the duration of treatment ( r= 0.49, P= 0.002), was found in children on sodium valproate without, however, a concomitant significant elevation of total AP values. We conclude that children who receive antiepileptic drugs as monotherapy, even when residing in a Mediterranean country with adequate sunlight, may have their bone metabolism affected as indicated by the elevated levels of bone AP isoenzyme. This isoenzyme, but not total AP values, could therefore be used as a marker for the selection of patients who would be benefited by a thorough evaluation of their bone metabolism profile.

Acute Necrotizing Encephalopathy Associated With Parainfluenza Virus in a Caucasian Child

Acute necrotizing encephalopathy is a severe parainfectious disorder with a clear racial predilection for Oriental children living in the Far East. The prognosis was originally reported as grave; however, a mild form of the disease has recently been described. A case of parainfluenza virus—associated acute necrotizing encephalopathy in a Caucasian child with a mild clinical course and excellent prognosis is presented. In this patient, the initial clinical picture was not very impressive, and the diagnosis was delayed until the third week of the illness, when neuroimaging was performed. Two months later, clinical and neuroimaging findings had almost completely resolved. Suggested criteria for a benign prognosis, such as normal liver function and cerebrospinal fluid protein levels, asymmetric thalamic lesions, and no brainstem involvement, were relevant in the present case. An extended diagnostic work-up for metabolic, vascular, coagulation, and infectious diseases was negative apart from a seroconversion for parainfluenza virus. To our knowledge, this is the first reported case of acute necrotizing encephalopathy associated with parainfluenza virus infection. Acute necrotizing encephalopathy, especially in the mild form, might not be fully recognized and could be underdiagnosed in Europe, where the reported incidence of the syndrome is very low. (J Child Neurol 2003;18:570—572).

Acute disseminated encephalomyelitis associated with parainfluenza virus infection of childhood

Acute disseminated encephalomyelitis associated with the parainfluenza virus has rarely been reported in childhood. A 2.5-year-old girl with acute disseminated encephalomyelitis, who developed bilateral symmetrical lesions in the basal ganglion, thalamus, corpus callosum, cerebral subcortical white matter, and cerebellar medulla on brain magnetic resonance imaging is described. Serological confirmation of parainfluenza virus infection was made 2 weeks following the onset of neurological symptoms. Four months later, the patient had a full recovery. At present, 3 years later, no relapse has been reported and she is leading a normal life. Our case is of interest because of its rarity, the striking brain magnetic resonance imaging, and the good neurological outcome.

Early Alteration in Bone Metabolism in Epileptic Children Receiving Carbamazepine Monotherapy Owing to the Induction of Hepatic Drug—Metabolizing Enzymes

The purpose of this study was to investigate, by a prospective, self-controlled method, whether early treatment with carbamazepine monotherapy can alter bone metabolism in ambulatory epileptic children with adequate sun exposure, based on the determination of total serum alkaline phosphatase and its bone isoenzyme activities. Serum total alkaline phosphatase and its bone, liver, and intestinal isoenzyme activities were evaluated in 22 epileptic ambulatory children (13 males and 9 females, aged from 5 to 12 years) before and at 3, 6, and 12 months of carbamazepine monotherapy. Serum concentrations of other biochemical markers of bone and liver metabolism, such as calcium, phosphorus, magnesium, γ-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase, were also measured in the study participants before and at 6 and 12 months of treatment. Carbamazepine was prescribed at normal dosages (16.4—20 mg/kg/day). Serum total alkaline phosphatase activities were significantly increased at 3 (P = .000), 6 (P = .024), and 12 (P = .037) months of treatment; serum bone alkaline phosphatase activities at 3 (P = .000), 6 (P = .008), and 12 (P = .017) months of treatment; and serum liver alkaline phosphatase activities at 3 (P = .000), 6 (P = .049), and 12 (P = .008) months of treatment, whereas serum intestinal alkaline phosphatase isoenzyme activity was significantly increased only at 3 months of treatment (P = .035). Serum γ-glutamyltransferase activities were also significantly increased at 6 (P = .000) and 12 (P = .000) months of treatment. No significant changes in the concentrations of serum calcium, phosphorus, magnesium, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase were noted at 6 and 12 months of treatment. There was a significant correlation between serum γ-glutamyltransferase activities and serum total alkaline phosphatase activities (r = .689, P = .000 at 6 months; r = .493, P = .020 at 12 months), bone alkaline phosphatase activities (r = .700, P = .000 at 6 months; r = .466, P = .029 at 12 months), and liver alkaline phosphatase activities (r = .427, P = .047 at 6 months; r = .425, P = .048 at 12 months). These findings indicate that ambulatory children who receive carbamazepine monotherapy, even when residing in a country with adequate sunlight, can have their bone metabolism altered early in the course of treatment, as indicated by the elevated activities of serum bone alkaline phosphatase isoenzyme. This early alteration in bone metabolism is probably due to the hepatic enzyme—inducing character of carbamazepine. (J Child Neurol 2005;20:513—516).

Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a rare cause of parainfectious rhabdomyolysis

Congenital cataracts-facial dysmorphism-neuropathy syndrome (CCFDN, MIM: 604168), is a recently delineated neurogenetic disease causing recurrent episodes of rhabdomyolysis; prevention and early diagnosis of rhabdomyolysis should be part of the clinical management of the disease.

Long-Term Findings on Brain Magnetic Resonance Imaging in Acute Encephalopathy With Bilateral Striatal Necrosis Associated With Measles

The long-term findings on brain magnetic resonance imaging (MRI) in a 710/12-year-old boy with a history of acute encephalopathy with bilateral striatal necrosis following measles at the age of 22 months are described. At the early stage of illness, brain MRI studies revealed bilateral, symmetric basal ganglia lesions, predominant on the globi pallidi, appearing as hyperintense signals on T1- and T2-weighted images. Six years later, follow-up brain MRI studies showed that the bilateral, symmetric lesions on the globi pallidi persisted with low signal on T1- and high signal on T 2weighted images. At present, the patient has some persistent neurologic signs. These findings suggest that both clinical and neuroradiologic findings may persist in children with acute encephalopathy with bilateral striatal necrosis following measles. (J Child Neurol 2002;17:776—777).

Congenital Microcephaly in Two Infants With the Factor V Leiden Mutation

Two infants with congenital microcephaly associated with the factor V Leiden mutation are described. In both cases, brain magnetic resonance imaging (MRI) revealed cerebral atrophy and porencephalic cystic lesions, which were probably attributable to prenatal cerebral vascular events. These findings suggest that assessment for this mutation is an important part of the evaluation of infants with unexplained congenital microcephaly, especially in cases with infarcts and/or porencephalic cysts on brain MRI. (J Child Neurol 2002;17:904—906).

A toddler with acute flaccid paralysis due to West Nile virus infection.

We report on a 2-year-old boy with acute flaccid paralysis due to West Nile neuroinvasive disease. Serum and cerebrospinal fluid serology as well as nerve conduction studies were consistent with the diagnosis. He received intravenous immunoglobulin and showed gradual improvement and complete recovery of his muscle strength, gait and deep tendon reflexes.