Oxidative Stress Markers and the Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) is a leading cause of potentially preventable blindness in low birth weight preterm infants. Several perinatal and postnatal factors contribute to the incomplete maturation of retinal vascularization, leading to oxidative stress damage. Literature data suggest that the lack of equilibrium between pro-oxidants and anti-oxidants plays a key role. In the last decade, there has been an increasing interest in identifying the antecedents of ROP and the relevant pathogenic mechanisms involved. In this context, a panel of biomarkers was investigated in order to achieve early detection of oxidative stress occurrence and to prevent retinal damage. Several nutritional elements have been found to play a relevant role in ROP prevention. At this stage, no conclusive data have been shown to support the usefulness of one biomarker over another. Recently, the Food and Drugs Administration, the European Medicine Agency, and the National Institute of Health proposed a series of criteria in order to promote the inclusion of new biomarkers in perinatal clinical guidelines and daily practice. The aim of the present review is to offer an update on a panel of biomarkers, currently investigated as potential predictors of ROP, highlighting their strengths and weaknesses.

Valproate in adolescents with photosensitive epilepsy with generalized tonic-clonic seizures only.

AIM: To assess the effects of valproate (VPA) on seizure response/control and photosensitivity (PS) in adolescents suffering from photosensitive epilepsy with generalized tonic-clonic seizures only (EGTCS). METHODS: We prospectively evaluated 55 adolescents with newly diagnosed EGTCS and PS at presentation, who received VPA monotherapy. Two phases of the study were defined and analysed separately. In the phase I, the electroclinical data of patients were compared over three time points: T1 (at 6 months of treatment); T2 (at 12 months of treatment); and T3 (at 36 months of treatment). In the phase II, only patients who stopped VPA were evaluated over a period of 12 months. RESULTS: At both T2 and T3 there was a significant great percentage of seizure-free patients compared with that at T1 (78.2% vs 69.1%, p < 0.01; and 85.5% vs 69.1%, p < 0.001) and a similar trend was also noted according to PS-free patients (70.9% vs 52.7%, p < 0.01; 80.0% vs 52.7% p < 0.001). At the end of the phase II, 46.5% and 32.6% out of 43 patients who stopped VPA had seizure relapses and reappearance of PS, respectively. In particular, 78.6% of the 14 patients with PS reappearance presented the same type of EEG response showed at study entry. CONCLUSIONS: VPA monotherapy is very effective for both seizure outcome control and PS reduction in adolescents with EGTCS. Treatment discontinuation induces relapse of seizures and PS in a certain number of patients. PS reappearance presented the same type of EEG response showed before VPA treatment.

Metabolic and endocrine effects of valproic acid chronic treatment.

Treatment of epileptic patients with valproic acid (VPA) may be associated with substantial weight changes that may increase morbidity and impair adherence to the treatment regimen. VPA-induced weight gain seems to be associated with many metabolic disturbances; the most frequent are hyperinsulinemia and insulin resistance, hyperleptinemia and leptin resistance. Patients who gain weight during VPA therapy can develop dyslipidemia and metabolic syndrome that are associated with long-term vascular complications such as hypertension and atherosclerosis. Moreover, an elevation in the levels of uric acid and homocysteine, together with oxidative stress, may contribute to atherosclerotic risk in patients under long-term therapy with VPA. The aim of this review is to discuss the metabolic and endocrine effects of VPA chronic treatment in patients with epilepsy.

Reflex myoclonic epilepsy in infancy: a multicenter clinical study.

PURPOSE: To describe the clinical and electroencephalographic (EEG) features of reflex myoclonic epilepsy in infancy (RMEI) and long-term cognitive outcome. METHODS: We enrolled 31 children from 16 neuropediatric centres in Italy, who underwent clinical and video-EEG evaluation. Cognitive assessment was performed in all patients using standardized psychometric tests. RESULTS: The age at onset ranged from 3 to 24 months of age. Seizures were characterised in all patients by symmetric myoclonic seizures (MS), triggered by sudden unexpected acoustic (38.7%) or tactile stimuli (29%) or both (29%). Spontaneous attacks were reported in 32.2% of the cases. Ictal EEG showed generalized high-amplitude 3 Hz polyspike and wave discharges, synchronous with brief rhythmic bursts of electromyographic activity. Patients were re-evaluated after a period of 7.2 ± 5.6 years. The prognosis for seizure control was excellent in all cases and reflex MS disappeared spontaneously or after valproate treatment. The cognitive outcome was excellent in 90.3% of children. CONCLUSIONS: RMEI appears to be a variety of idiopathic generalized epilepsy with specific features that occurs in developmentally normal children.

Diagnosis and management of catamenial seizures: a review.

Catamenial epilepsy is defined as a pattern of seizures that changes in severity during particular phases of the menstrual cycle, wherein estrogens are proconvulsant, increasing the neuronal excitability; and progesterone is anticonvulsant, enhancing GABA-mediated inhibition. Thus, changes in serum estradiol/progesterone ratio throughout a normal reproductive cycle bring about an increased or decreased risk of seizure occurrence. To date, there are no specific drug treatments for catamenial epilepsy however, non-hormonal and hormonal therapies have been proposed. The aim of this review is to report preclinical and clinical evidences about the relationship between female reproductive steroids and epileptic seizures, and to describe treatment approaches for catamenial epilepsy.

Long-term outcome of epilepsy in Kabuki syndrome.

UNLABELLED: PURPOSES AND METHODS: Kabuki syndrome (KS) is a rare dysmorphic disorder characterized by multiple congenital anomalies and mental retardation. Although epilepsy is one of the most common clinical complications associated with KS, few studies have evaluated its electroclinical aspects and long-term outcome. Therefore, we describe here a clinical series of 10 Caucasian KS patients who developed epilepsy in childhood. We followed all children for at least 5 years. RESULTS: All patients presented partial seizures and interictal EEGs revealed focal epileptic paroxysms with prevalent involvement of temporo-occipital areas. Seven children had no central nervous system abnormalities, but enlargement of lateral ventricles, corpus callosum hypoplasia, and adenohypophysis hypoplasia were revealed in three. Although antiepileptic drug (AED) treatment was effective in controlling seizures and normalizing EEG abnormalities in 8 patients, the other 2 cases were resistant to multiple AEDs. In one of these two patients, withdrawal of AED resulted in status epilepticus and death. CONCLUSIONS: Partial seizures and temporo-occipital abnormalities on interictal EEG are common features of KS patients who suffer from epilepsy. Prognosis of this epilepsy is favourable in the majority of cases with complete disappearance of seizures and EEG abnormalities.

Antiepileptic drugs, sex hormones, and PCOS.

Reproductive endocrine dysfunction in women with epilepsy is an important issue, and in recent years there is growing evidence to support the effect on sex hormones of both epilepsy per se and various antiepileptic drugs (AEDs). Focal epileptic discharges from the temporal lobe may have a direct influence on the function of the hypothalamic-pituitary axis, thereby altering the release of sex steroid hormones. The role of laterality and severity of epilepsy is still conflicting. The use of the liver enzyme-inducing AEDs--such as phenobarbital, phenytoin, and carbamazepine--can increase serum sex hormone-binding globulin concentrations, leading to diminished bioactivity of testosterone (T) and estradiol. Valproic acid, an enzyme inhibitor, has been associated with the occurrence of reproductive endocrine disorders characterized by high serum T, free androgen index, androstenedione, dehydroepiandrosterone sulfate concentrations, and with polycystic changes in ovaries and menstrual disorders. A better understanding of the effects of AEDs on sex hormones is key to selecting the appropriate AEDs and is crucial for reproductive health in female patients.

Gastaut type-idiopathic childhood occipital epilepsy and childhood absence epilepsy: a clinically significant association?

We report an unusual association between idiopathic occipital epilepsy and childhood absence epilepsy in 2 pediatric patients. At first clinical and electroencephalographic evaluation, the patients presented the peculiar signs of idiopathic occipital epilepsy Gastaut type: focal sensory visual seizures, migraine-like symptoms (only in one patient) and unilateral spike-wave discharges over occipital regions. Both children were treated with valproic acid and their seizures were rapidly controlled. After a seizure-free period, the patients presented typical absence with ictal electroencephalographies showing 3 cycles/s generalized and symmetrical spike-wave complexes. We discuss the possible association between these two epileptic syndromes and its common pathophysiological mechanisms.

Epilepsy, sex hormones and antiepileptic drugs in female patients.

Women with epilepsy have a higher incidence of reproductive endocrine disorders than the general female population. These alterations include polycystic ovary syndrome, hyperandrogenemia, infertility, hypothalamic amenorrhea and hyperprolactinemia. Reproductive dysfunction is attributed both to epilepsy itself and to antiepileptic drugs (AEDs). Focal epileptic discharges from the temporal lobe may have a direct influence on the function of the hypothalamic-pituitary axis, thus altering the release of sex steroid hormones, including the production of luteinizing hormone, follicle-stimulating hormone, gonadotropin-releasing hormone and prolactin. AEDs may modulate hormone release from the hypothalamic-pituitary-gonadal axis and they may alter the metabolism of sex hormones and their binding proteins. Hepatic enzyme-inducing AEDs, such as carbamazepine and phenytoin, may be most clearly linked to altered metabolism of sex steroid hormones, but valproic acid, an enzyme inhibitor, has also been associated with a frequent occurrence of polycystic ovary syndrome and hyperandrogenism in women with epilepsy. Therefore, treatment of epilepsy and selection of AEDs are important for reproductive health in female patients. The aim of the present review is to critically evaluate the recently published data concerning the interactions between sex hormones, epilepsy and AEDs.