Sotiria Mastroyianni

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.

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).

MKS1 regulates ciliary INPP5E levels in Joubert syndrome

Background Joubert syndrome (JS) is a recessive ciliopathy characterised by a distinctive brain malformation ‘the molar tooth sign’. Mutations in >27 genes cause JS, and mutations in 12 of these genes also cause Meckel-Gruber syndrome (MKS). The goals of this work are to describe the clinical features of MKS1-related JS and determine whether disease causing MKS1 mutations affect cellular phenotypes such as cilium number, length and protein content as potential mechanisms underlying JS. Methods We measured cilium number, length and protein content (ARL13B and INPP5E) by immunofluorescence in fibroblasts from individuals with MKS1-related JS and in a three-dimensional (3D) spheroid rescue assay to test the effects of disease-related MKS1 mutations. Results We report MKS1 mutations (eight of them previously unreported) in nine individuals with JS. A minority of the individuals with MKS1-related JS have MKS features. In contrast to the truncating mutations associated with MKS, all of the individuals with MKS1-related JS carry ≥1 non-truncating mutation. Fibroblasts from individuals with MKS1-related JS make normal or fewer cilia than control fibroblasts, their cilia are more variable in length than controls, and show decreased ciliary ARL13B and INPP5E. Additionally, MKS1 mutant alleles have similar effects in 3D spheroids. Conclusions MKS1 functions in the transition zone at the base of the cilium to regulate ciliary INPP5E content, through an ARL13B-dependent mechanism. Mutations in INPP5E also cause JS, so our findings in patient fibroblasts support the notion that loss of INPP5E function, due to either mutation or mislocalisation, is a key mechanism underlying JS, downstream of MKS1 and ARL13B.

Anti-N-methyl-D-aspartate receptor encephalitis presenting with acute psychosis in a preteenage girl: a case report

IntroductionAnti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a rare, newly defined autoimmune clinical entity that presents with atypical clinical manifestations. Most patients with anti-N-methyl-D-aspartate receptor encephalitis develop a progressive illness from psychosis into a state of unresponsiveness, with catatonic features often associated with abnormal movements and autonomic instability. This is the first report of anti-N-methyl-D-aspartate receptor encephalitis in a Greek pediatric hospital.Case presentationAn 11-year-old Greek girl presented with clinical manifestations of acute psychosis. The differential diagnosis included viral encephalitis. The presence of a tumor usually an ovarian teratoma, a common clinical finding in many patients, was excluded. Early diagnosis and prompt immunotherapy resulted in full recovery up to one year after the initial diagnosis.ConclusionAcute psychosis is a rare psychiatric presentation in children, diagnosed only after possible organic syndromes that mimic acute psychosis are excluded, including anti-N-methyl-D-aspartate receptor receptor encephalitis. Pediatricians, neurologists and psychiatrists should consider this rare clinical syndrome, in order to make an early diagnosis and instigate appropriate treatment to maximize neurological recovery.

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.

Moya Moya Syndrome in a Child With Pyruvate Kinase Deficiency and Combined Prothrombotic Factors

A 13-year-old Greek girl with pyruvate kinase deficiency and moya moya angiographic pattern is reported. She also had raised serum lipoprotein (a) concentration and was homozygous for the C677T mutation of the methylenetetrahydrofolate reductase gene. She presented with neonatal onset of anemia, hemolytic and aplastic crises, especially during infections, stroke, and also progressive motor and mental deterioration. A digital cranial angiography at 13 years revealed the typical angiographic findings of moya moya angiopathy. This is likely the first patient with pyruvate kinase deficiency and moya moya syndrome and also the combination of elevated serum lipoprotein (a) concentration and the C677T mutation of the methylenetetrahydrofolate reductase gene to be reported. In patients with pyruvate kinase deficiency and moya moya syndrome, a search for raised serum lipoprotein (a) concentrations and the C677T mutation of the methylenetetrahydrofolate reductase gene should be considered.

Different Additional Risk Factors for Cerebral Infarctions Associated With the Factor V Leiden Mutation in a Family

Several cases with cerebral infarctions associated with the factor V Leiden mutation have been reported. However, bearing in mind the large number of asymptomatic individuals with the factor V Leiden mutation, additional risk factors for cerebral infarctions should be considered. In this report, two siblings with cerebral infarctions associated with a combination of heterozygous factor V Leiden mutation and different additional exogenous and endogenous thrombogenic risk factors are described. Respiratory problems in the perinatal period and increased lipoprotein (a) concentrations in the first patient and an episode of gastroenteritis from Shigella infection and persistent high titers of serum anticardiolipin and β2-glycoprotein I antibodies in the second patient were recorded as additional thrombogenic risk factors. Furthermore, both patients were found to be heterozygous for the methylenetetrahydrofolate reductase gene C677T mutation. These findings suggest that even in the same family, different additional thrombogenic risk factors can be present in infants with cerebral infarctions associated with the factor V Leiden mutation. An extensive search of additional circumstantial and genetic thrombogenic risk factors should be useful for prophylaxis and prognosis of these infants with cerebral infarctions associated with the factor V Leiden mutation and of their related family members. To our knowledge, the second patient in this study is the first patient reported to have cerebral infarctions associated with the combination of the factor V Leiden mutation and persistent high titers of serum β2-glycoprotein I antibodies. (J Child Neurol 2006;21:903—907; DOI 10.2310/7010.2006.00198).

Infantile spasms in an infant with cytomegalovirus infection treated with ganciclovir.

A 3-month-old male infant with cytomegalovirus infection and intractable partial seizures was treated with ganciclovir for 6 weeks. The drug was well tolerated, and virus shedding in the cerebrospinal fluid and urine was eliminated, although infantile spasms at the age of 6 months appeared. At the age of 12 months, intractable seizures persisted, and the psychomotor development of the infant was markedly delayed. To our knowledge, no previous similar case has been reported. These findings suggest that treatment with ganciclovir of infants with cytomegalovirus infection results only in cessation of virus shedding in the cerebrospinal fluid and urine without having a preventive effect on the future appearance of infantile spasms. This may be due to the irreversibility of previous brain damage from the cytomegalovirus infection and the virostatic nature of the drug. (J Child Neurol 2004;19:50—53).

The challenges that parents of children with epilepsy face: A qualitative study

OBJECTIVE This qualitative study explored the challenges that Greek parents/caregivers of children with controlled epilepsy (CwE) face regarding the disorder. METHODS Interviews were conducted based on open-ended questions guided by a review of the literature. A total of 91 parents/caregivers were recruited by neurologists at the neurology clinics of two Athens public hospitals. A hermeneutic phenomenological approach was used to explore parent/caregiver experiences. The data were grouped and analyzed through a textual interpretation. RESULTS Two key challenges were identified for parents of CwE: the disclosure of epilepsy and the absence of adequate information about coping with epilepsy. Parents in Greece were hesitant to reveal their childs epilepsy to school staff and their wider social milieu. Also, although satisfied with the patient-centered approach they experienced with their hospital doctor, parents/caregivers found that they needed more education about the existing sources of psychosocial and emotional support to cope with their childs epilepsy personally and as a family. Finally, the parents/caregivers who let their child know about the epilepsy and discussed the implications with the child found that parent-child communication improved. CONCLUSION This study provides valuable insight into the impact of epilepsy on parents of CwE, which might help hospital and school staff support families with greater understanding, sensitivity, and skill. The findings suggest that Greek authorities should staff hospitals and schools with experts and more systematically advertise sources of information about epilepsy and ways to cope with it.