Feto-Placental Atherosclerotic Lesions in Intrauterine Fetal Demise: Role of Parental Cigarette Smoking

The atherogenic effect of cigarette smoking is already recognizable in coronary arteries of fetuses in the last gestational weeks. In this study we analyzed the atherogenic effect of mother’s and father’s smoking habit on coronary arteries and even on adnexa of 30 human fresh fetuses died from 32 to 41 gestational weeks. In 12 cases only the mothers of the victims were cigarette smokers, in 7 cases only the fathers were smokers, whereas in 11 cases nobody smoked

Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is an autosomal recessive condition due to a deficiency of α-aminoadipic semialdehyde dehydrogenase, which is a key enzyme in lysine oxidation. PDE-ALDH7A1 is a developmental and epileptic encephalopathy that was historically and empirically treated with pharmacologic doses of pyridoxine. Despite adequate seizure control, most patients with PDE-ALDH7A1 were reported to have developmental delay and intellectual disability. To improve outcome, a lysine-restricted diet and competitive inhibition of lysine transport through the use of pharmacologic doses of arginine have been recommended as an adjunct therapy. These lysine-reduction therapies have resulted in improved biochemical parameters and cognitive development in many but not all patients. The goal of these consensus guidelines is to re-evaluate and update the two previously published recommendations for diagnosis, treatment, and follow-up of patients with PDE-ALDH7A1. Members of the International PDE Consortium initiated evidence and consensus-based process to review previous recommendations, new research findings, and relevant clinical aspects of PDE-ALDH7A1. The guideline development group included pediatric neurologists, biochemical geneticists, clinical geneticists, laboratory scientists, and metabolic dieticians representing 29 institutions from 16 countries. Consensus guidelines for the diagnosis and management of patients with PDE-ALDH7A1 are provided. This article is protected by copyright. All rights reserved

Antenatal treatment in two Dutch families with pyridoxine-dependent seizures

Contains fulltext : 88199.pdf (publisher's version ) (Closed access)Incidental reports suggest that antenatal treatment of pyridoxine dependent seizures (PDS) may improve neurodevelopmental outcome of affected patients. Two families with PDS are reported, both with two affected siblings. Antenatal treatment with pyridoxine was instituted during the second pregnancy in each family (50 and 60 mg daily from 3 and 10 weeks of gestation, respectively). Perinatal characteristics and neurodevelopmental outcome at 4 (Family A) and 12 (Family B) years of age were compared between the untreated and treated child within each family. Meconium-stained amniotic fluid was present in both first pregnancies and abnormal foetal movements were noticed in one. In the treated infants, pregnancy and birth were uncomplicated. In family A, postnatal pyridoxine supplementation prevented neonatal seizures. Both children in family A were hypotonic and started walking after 2 years of age; both had white matter changes on MRI, and the first child was treated for squint. IQ was 73 and 98 in the antenatally untreated and treated child, respectively. The second child in family B developed seizures on the seventh day, because pyridoxine maintenance therapy had not been instituted after birth. Seizures responded rapidly to pyridoxine supplementation. MRI showed large ventricles and a mega cisterna magna. IQ was 80 and 106 in the antenatally untreated and treated child respectively. Both children had normal motor development. These results suggest that antenatal pyridoxine supplementation may be effective in preventing intrauterine seizures, decreasing the risk of complicated birth and improving neurodevelopmental outcome in PDS.1 maart 201

Pyridoxine-dependent epilepsy initially responsive to phenobarbital Epilepsia por dependência de piridoxina inicialmente responsiva ao fenobarbital

Pyridoxine-dependent epilepsy is a rare autossomal recessive disorder characterized by recurrent seizures that are not controlled by anticonvulsant medications but remits after administration of pyridoxine. We report on a 30 day-old girl who presented with seizures during the first day of life, initially responsive to anticonvulsant therapy, which remitted within two weeks. Seizures were characterized as multifocal myoclonic jerks of upper and lower limbs associated with buccal-lingual oral movements and eyelid blinking. Laboratory and neuroimaging studies were normal. Electroencephalographic record demonstrated a abnormal background activity with high-voltage epileptic discharges and a burst-suppression pattern. The seizures ceased after oral administration of pyridoxine, but recurred after withdrawal, confirming the diagnosis.<br>A epilepsia por dependência de piridoxina é uma doença autossômica recessiva rara caracterizada por crises recorrentes refratárias a tratamento medicamentoso, mas que remitem após a administração de piridoxina. Relatamos o caso de menina de 30 dias de vida que iniciou crises convulsivas desde o primeiro dia de vida, inicialmente responsivas a tratamento com drogas anticonvulsivantes, mas que reiniciaram após a segunda semana de vida. As crises eram caracterizadas por movimentos clônicos erráticos de membros superiores e inferiores associados a movimentos oromandibulares e piscamentos. Exames laboratoriais e de neuroimagem foram normais. O exame eletrencefalográfico evidenciou atividade de base desorganizada com descargas epilépticas de alta voltagem associadas a um padrão de surto-supressão. As crises cessaram após a administração de piridoxina e recorreram após a sua retirada, confirmando o diagnóstico

Diagnostic Approach to Genetic Causes of Early-Onset Epileptic Encephalopathy

Epileptic encephalopathies are characterized by recurrent clinical seizures and prominent interictal epileptiform discharges seen during the early infantile period. Although epileptic encephalopathies are mostly associated with structural brain defects and inherited metabolic disorders, pathogenic gene mutations may also be involved in the development of epileptic encephalopathies even when no clear genetic inheritance patterns or consanguinity exist. The most common epileptic encephalopathies are Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, West syndrome and Dravet syndrome, which are usually unresponsive to traditional antiepileptic medication. Many of the diagnoses describe the phenotype of these electroclinical syndromes, but not the underlying causes. To date, approximately 265 genes have been defined in epilepsy and several genes including STXBP1, ARX, SLC25A22, KCNQ2, CDKL5, SCN1A, and PCDH19 have been found to be associated with early-onset epileptic encephalopathies. In this review, we aimed to present a diagnostic approach to primary genetic causes of early-onset epileptic encephalopathies