NADPH oxidase activation and 4-hydroxy-2-nonenal/aquaporin-4 adducts as possible new players in oxidative neuronal damage presents in drug-resistant epilepsy.

A correlation between epilepsy and cellular redox imbalance has been suggested, although the mechanism by which oxidative stress (OS) can be implicated in this disorder is not clear. In the present study several oxidative stress markers and enzymes involved in OS have been determined. In particular, we examined the levels of 4-hydroxy-2-nonenal protein adducts (HNE-PA), a by-product of lipid peroxidation, and the activation of NADPH oxidase 2 (NOX2), as cellular source of superoxide (O(2)(-)), in surgically resected epileptic tissue from drug-resistant patients (N=50). In addition, we investigated whether oxidative-mediated protein damage can affect aquaporin-4 (AQP4), a water channel implicated in brain excitability and epilepsy. Results showed high levels of HNE-PA in epileptic hippocampus, in both neurons and glial cells and cytoplasmic positivity for p47(phox) and p67(phox) suggesting NOX2 activation. Interestingly, in epileptic tissue immunohistochemical localization of AQP4 was identified not only in perivascular astrocytic endfeet, but also in neurons. Nevertheless, negativity for AQP4 was observed in neurons in degeneration. Of note, HNE-mediated post-translational modifications of AQP4 were increased in epileptic tissues and double immunofluorescence clearly demonstrated co-localization of AQP4 and HNE-PA in epileptic hippocampal structures. The idea is that sudden, disorderly, and excessive neuronal discharges activates NOX2 with O(2)(-) production, leading to lipid peroxidation. The resulting generation of HNE targets AQP4, affecting water and ion balance. Therefore, we suggest that seizure induces oxidative damage as well as neuronal loss, thereby promoting neuronal hyperexcitability, also affecting water and ion balance by AQP4 modulation, and thus generating a vicious cycle.

Intrinsic cerebral connectivity analysis in an untreated female-to-male transsexual subject: a first attempt using resting-state fMRI.

BACKGROUND/AIMS: Transsexualism is a gender identity disorder whose symptomatology could involve cognitive, neurobiological and psychological variance from biological sex standard. Several evidences support the hypothesis of a structural and functional brain reorganization in transgender subjects, with a different impact for male-to-female and female-to-male (FtM) subjects. Here we used resting-state fMRI to understand the similarities between the spontaneous brain connectivity of an untreated FtM subject and two male and female control groups. METHODS: Both seed-voxel and atlas-based region-of-interest (ROI) approaches were used. RESULTS: Brain areas sensitive to gender dimorphism like left lingual gyrus and precuneus showed strong similarities between the FtM subject and female control group with respect to control males, with comparable extension and location of functional connectivity maps. ROI analysis confirmed this evidence, highlighting a greater pattern of differences between the FtM subject and males and the FtM subject and females. No difference between seed-voxel results in the FtM subject and females was found. CONCLUSION: These data partially support the idea that untreated FtM transgender shows a functional connectivity profile comparable to female control subjects.

Oxcarbazepine and atypical evolution of benign idiopathic focal epilepsy of childhood.

Patients that have benign epilepsy with centrotemporal spikes (BECTS) may occasionally experience an atypical development in their course when treated with drugs such as carbamazepine. Three patients with electroclinical patterns consistent with BECTS showed seizure exacerbation during oxacarbazepine (OXC) therapy. Two manifested atypical absences, neuropsychological disturbances, and generalized spike-and-wave discharges in their electroencephalograms (EEGs) that became continuous during sleep. The third patient showed, during OXC therapy, more frequent partial motor seizures which ended with ictal vomiting and post-ictal obnubilation. EEGs recorded during sleep showed discontinuous paroxysmal activity in the right centrotemporal area. Symptoms were reversed following discontinuation of the OXC therapy. Although electroclinical findings were consistent with a BECTS diagnosis, all patients had some atypical features. Our observations show that BECTS patients, in particular those presenting with atypical findings, might be at risk for developing paradoxical reactions to OXC therapy. We suggest that OXC should be included in the list of drugs that may cause electroclinical deterioration in these patients.

Malformations of cortical development in neurofibromatosis type 1.

The authors report three patients with neurofibromatosis type 1 and different types of malformations of cortical development: Patient 1 had a possible transmantle cortical dysplasia involving the right temporoinsuloparieto-occipital areas; Patient 2 had a periventricular band of heterotopic gray matter with an overlying pachygyric cerebral cortex; and Patient 3 had a left perisylvian polymicrogyria. Because all of these lesions result from different pathogenetic mechanisms, neurofibromin may play a role during several stages of cortical development.

Septo-optic dysplasia with digital anomalies associated with maternal multidrug abuse during pregnancy.

We describe a 16-year-old female affected by septo-optic dysplasia (SOD) with digital anomalies as additional feature. This rare developmental anomaly of midline brain structures can result from different pathogenetical events, including mutations of the homeo box gene HESX1, recently suggested as the etiological cause at least in a subset of patients. The absence of mutational involvement of this gene in our patient led us to consider, in alternative terms of pathogenesis, the maternal multidrug abuse occurring during pregnancy. Our report, in accord with previous experimental evidences, points out that illicit drug use might have played a causative role in brain development anomalies, thus our patient could represent an additional case of birth defects caused by a prenatal toxic exposure. The neurologic abnormalities and the clinical history of the patient are extensively reviewed. The need to include the SOD phenotype amongst the possible teratogenic effects of multidrug abuse is evidenced.

Landau-Kleffner syndrome (LKS): long-term follow-up and links with electrical status epilepticus during sleep (ESES).

We describe 11 patients affected by Landau-Kleffner syndrome (LKS) with a mean follow-up of 9 years and 8 months. EEG recordings during wakefulness, NREM and REM sleep showed a bitemporal electrical status epilepticus during sleep (BTESES) in all cases; four of them presented a shift from a BTESES towards an 'intercalated electrical status epilepticus during sleep' (IESES) accompanied by a global regression of cognitive and behavioural functions in 3/4 of cases. At the last observation, only 18.2% of cases presented a complete language recovery and mental retardation was evident in 63.6%. The prognosis of LKS in our cases may depend on the interaction of different negative factors such as onset of aphasia before 4 years, its duration for longer than 1 year, long-lasting duration and continuity without fluctuations of BTESES/IESES, probably preexisting mild speech delay. It is important for the prognosis to utilize antiepileptic treatment and possibly neurosurgical techniques to eliminate EEG paroxysmal abnormalities. At present, no similar cases with clinical-EEG evolution from LKS to electrical status epilepticus during sleep (ESES) have ever been described. Our observation demonstrates that LKS and ESES classified as different clinical-EEG syndromes represent two aspects of the same brain dysfunction and they may exist separately or pass one into the other with a change in the clinical-EEG picture. The common origin of the two syndromes is confirmed by recent functional brain imaging, neurophysiological and neurosurgical techniques.

Quantitative EEG mapping, regional cerebral blood flow, and neuropsychological function in Alzheimer's disease.

The relations between quantitative EEG, regional cerebral blood flow (rCBF), severity of disease and neuropsychological data were analyzed in 31 patients in different stages of Alzheimer's disease (AD). As a group the demented patients had higher delta and theta activities, lower alpha activity and lower alpha peak frequency than control subjects. rCBF was reduced in all regions studied but mainly in the temporoparietal areas. An analysis of correlations showed a close relationship between rCBF and certain quantitative EEG parameters in AD patients, mainly the power of the theta and delta bands. Both rCBF evaluation and quantitative EEG provide functional information related to the severity of cognitive impairment.

[CAT and MRI in the study of partial epilepsy: comparison of the 2 methods and correlations with EEG]. / TAC e RMN nello studio delle epilessie parziali: confronto tra le due metodiche e correlazioni con l'EEG.

Seventy five adult patients suffering from partial epilepsy were investigated by MRI. Results were then compared with those obtained with CT scan and EEG analysis. The interval between the two neuroradiological studies did not exceed five years. MRI and CT showed abnormalities respectively in 45 and 55% of patients, MRI showed a better sensitivity in detecting ischemic or atrophy-gliosis chronic focal alterations. In the remaining lesions such as tumors, vascular malformations, cysts and diffuse atrophies, where often an urgent diagnosis is necessary, both tests were equally sensitive. EEG showed alterations in 80% of patients and agreed with results of CT scan and MRI in about 80% of cases.