Epilepsy, unawareness of seizures and driving license: the potential role of 24-hour ambulatory EEG in defining seizure freedom.

INTRODUCTION: Seizures represent a potential source of accidents/death. Permission to drive may, therefore, be granted in a seizure-free period. Laws and regulations regarding this issue vary widely, and the onus of reporting seizures ultimately rests on the individual. Unfortunately, as some patients are unaware of their seizures, their reports may be unreliable. METHODS: In this retrospective study, we selected, from a group of 1100 consecutive patients, 57 cases (26 males/31 females; mean age: 42.5 years) in whom the AEEG documented ictal events (UIEs) not reported in a self-kept diary. By means of a simple questionnaire, we interviewed all these patients to collect information on driving licenses. We, thus, assessed how many of these patients (both drug resistant and seizure free) drove regularly. RESULTS: Our study shows a relatively large number of patients with epilepsy and UIEs. Fifteen patients suffered from idiopathic generalized epilepsy (IGE) while 42 had partial epilepsy (PE). The patients were seizure free in 21 cases and 36 had drug-resistant seizures. Many patients in both these subgroups had a driving license and drove normally (active driving in 12/36 drug-resistant patients and in 18/21 seizure-free patients). Worthy of note is the finding that an "apparently" seizure-free group of patients drove regularly. CONCLUSIONS: This study revealed a large number of patients (both drug resistant and seizure free) with AEEG-documented UIEs. This finding highlights the usefulness of AEEG in clinical practice as a means of more accurately ascertaining seizure freedom and supporting decisions involving the renewal or granting of a driving license.

LSD1-mediated demethylation of histone H3 lysine 4 triggers Myc-induced transcription.

Myc is a transcription factor that significantly contributes to cancer progression by modulating the expression of important genes through binding to a DNA sequence, CACGTG, called E-box. We find that on Myc binding to chromatin, the lysine-demethylating enzyme, LSD1, triggers a transient demethylation of lysine 4 in the histone H3. In addition, we demonstrate that Myc binds and recruits LSD1 to the E-box chromatin and the formation of this complex is stimulated by cAMP-PKA. Demethylation by LSD1 produces H(2)O(2), which locally oxidizes guanine and induces the recruitment of 8-oxoguanine-DNA glycosylase (OGG1) and of the nuclease Ape1 on the E-box chromatin. Inhibition of oxidation or silencing of LSD1, OGG1 or Ape1 significantly reduce transcription and inhibit mRNA accumulation of Myc-target genes. Collectively, these data highlight the role of transient LSD1-mediated demethylation of H3K4 leading to local DNA oxidation as driving force in the assembly of the Myc-induced transcription initiation complex.

Lithium prevents colchicine-induced apoptosis in rat cerebellar granule neurons.

OBJECTIVES: Here we evaluated the neuroprotective effects of two well-known mood stabilizers, lithium and valproic acid (VPA), against colchicine neurotoxicity in cerebellar granule cells (CGNs). METHODS: The CGNs were differentiated for 7 days, pretreated with lithium or VPA for 24 h and after colchicine 1 microM was added. Cellular damage was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) method and apoptosis in CGNs was characterized by chromatin condensation and DNA fragmentation. RESULTS: Incubation with lithium (1-5 mM) attenuated this apoptosis markedly, in a dose-dependent way however, the addition of VPA (0.5-2 mM) did not protect CGNs. Colchicine-induced apoptosis is mediated through the activation of caspase-3. An increase in caspase-3 activity was detected within 18 h and was blocked in presence of lithium 5 mM. CONCLUSIONS: Our data indicate that lithium treatment is selectively neuroprotective; however, in our experimental conditions VPA did not protect CGNs from apoptosis induced by colchicine. Our results support the hypothesis that distinct pathways mediate the neuroprotective effects of lithium and VPA.

Risk-factors for Parkinson's disease: case-control study in the province of Cáceres, Spain.

This case-control study, performed in a mixed rural and urban province, of 74 patients with Parkinson's disease (PD) and 148 unselected age and sex-matched controls, attempted to look possible risk factors for PD. Rural living, well-water drinking, positive family history for PD and postural tremor, were associated to an increased risk for PD, with results regarding exposure to pesticides near to statistical significance. Alcohol-drinking habit in males were associated to a decreased risk for PD, with results regarding cigarette-smoking habit in males near to statistical significance. We did not find association between the risk for PD and the following variables: 1) exposure to industrial toxins; 2) agricultural work; 3) cranial trauma; 4) previous common illnesses including some infections, arterial hypertension, diabetes mellitus, coronary heart disease and thyroid disease; 5) coffee and tea drinking habits.