The genetics of monogenic idiopathic epilepsies and epileptic encephalopathies.

The group of idiopathic epilepsies encompasses numerous syndromes without known organic substrate. Genetic anomalies are thought to be responsible for pathogenesis, with a monogenic or polygenic model of inheritance. Over the last two decades, a number of genetic anomalies and encoded proteins have been related to particular idiopathic epilepsies and epileptic encephalopathies. Most of these mutations involve subunits of neuronal ion channels (e.g. potassium, sodium, and chloride channels), and may result in abnormal neuronal hyperexcitability manifesting with seizures. However non-ion channel proteins may also be affected. Correlations between genotype and phenotype are not easy to establish, since genetic and non-genetic factors are likely to play a role in determining the severity of clinical features. The growing number of discoveries on this topic are improving classification, prognosis and counseling of patients and families with these forms of epilepsy, and may lead to targeted therapeutic approaches in the near future. In this article the authors have reviewed the main genetic discoveries in the field of the monogenic idiopathic epilepsies and epileptic encephalopathies, in order to provide epileptologists with a concise and comprehensive summary of clinical and genetic features of these seizure disorders.

Perinatal Hypoxic-Ischemic Encephalopathy: epileptic and paretic outcome at one year of age.

BACKGROUND: The issue concerning neurologic outcome in patients with perinatal Hypoxic-Ischemic Encephalopathy (H.I.E) has inspired many studies which tried to identify adequate prognostic factors. Our work aims to find among neonatal parameters:- factors which help to predict the risk to develop both Cerebral Palsy (CP) and secondary Epilepsy at one year of age in subjects affected by perinatal Hypoxic-Ischemic Encephalopathy,- correlations between the neonatal parameters and the variable severity of above mentioned sequelae. METHODS: We have recruited 32 subjects, whose history and neuroimages suggested a perinatal H.I.E and we have retrospectively analysed clinical-instrumental parameters at birth and at one year of age. RESULTS: At one year cut-off, 9 patients developed both secondary epilepsy and CP (28%), whereas the other subjects showed only motor delay (31%), only secondary epilepsy (3%) or only CP (38%). Patients with both the severest sequelae were essentially term infants (only 2/9 were pre-term infants), with normal weight (only 3 LBW) and 7 of them with early pathologic EEG and neuroimages pointing out cortex injuries (typical of term infants). A statistic analysis showed the following correlations: birth weight and global prognosis (chi2 = 14,03; p = 0,04); neonatal clinical pattern and CP's severity (chi2 = 14,03; p = 0,0009); early EEG and CP's severity (chi2 = 4,32; p = 0,04); epileptic onset age and CP and Epilepsy's severity (F = 16,01; p = 0,005).Birth weight represented a predictive factor of early neurological outcome (<1,5 kg birth weight neonates are not at risk of both epilepsy and CP); neonatal clinical pattern and early EEG were correlated with variable severity of CP; an epileptic exordium in the first 6 months led up to a more severe epileptic and paretic outcome. CONCLUSION: From a clinical point of view it is of crucial importance to have some parameters which enable to discriminate patients at risk of more severe sequelae from those at risk of moderate severity outcome.

Spatial working memory deficits in children at ages 3-4 who were low birth weight, preterm infants.

The aim of this study was to investigate attention and perceptual and spatial working memory abilities in preterm, low birth weight preschool children without evident brain disorders as determined by normal cerebral ultrasound findings and normal motor development. The authors evaluated 19 preterm and 19 typically developing children who were matched for IQ and chronological age. Results indicated that children born prematurely without major neurological deficits and with a normal cognitive level may have specific difficulty in sustained attention, visuospatial processing, and spatial working memory when evaluated at ages 3-4. This finding is relevant for understanding the qualitative aspects of cognitive development in preterm children and the neurobiological substrate underlying this development.

Factors predictive of seizures and neurologic outcome in perinatal depression.

To identify which early clinical variables are predictive of outcome in newborns with perinatal depression, we prospectively examined newborns with persistently abnormal neurologic examinations at 48 hours and (1) arterial pH

Neonatal seizures: characteristics of EEG ictal activity in preterm and fullterm infants.

The neonatal EEG remains one of oldest, yet most valuable, diagnostic and prognostic tests in neonates. The goals of this study were to determine the relationships between the morphology, frequency, and distribution of ictal discharges in the neonatal EEG with age, EEG background activity, and etiology. A total of 156 ictal events were evaluated in 11 preterm (PT) and 25 fullterm (FT) infants. Most of the infants had severe abnormalities of background activity although ictal discharges occurred on both normal and abnormal backgrounds. There was a trend for a closer relationship between behavioral changes during the electroencephalographic seizure when the background activity was normal or moderately abnormal than when background activity was severely abnormal. In both PT and FT infants, the most common site of seizure origin was the temporal lobe. FT infants commonly had sharp waves, spikes, sharp and slow waves, and spike and slow waves at the onset of the ictus while rhythmic delta activity was most common in the PT infants. PT infants typically had a regional onset to the ictus whereas FT infants most frequently had a focal onset. Duration of the ictal events was similar in PT and FT infants and a change in morphology or frequency of the discharges was common during propagation of the ictal discharges in both age groups. There was not a clear relationship between onset, morphology, frequency, or propagation patterns and etiology in either the PT or FT infants. Our results demonstrate that while the type of ictal discharge is related to gestational age, there is a rich variety in the onset, morphology, and frequency of the ictal discharges in both PT and FT infants and that neonatal ictal patterns lack a close correlation with underlying pathology.