EEG mean frequency changes in healthy subjects during prefrontal transcranial direct current stimulation.

In this pilot study we evaluated electroencephalographic (EEG) mean frequency changes induced by prefrontal transcranial direct current stimulation (tDCS) and investigated whether they depended on tDCS electrode montage. Eight healthy volunteers underwent tDCS for 15 min during EEG recording. They completed six tDCS sessions, 1 wk apart, testing left and right direct current (DC) dipole directions with six different montages: four unipolar montages (one electrode on a prefrontal area, the other on the opposite wrist) and two bipolar montages (both electrodes on prefrontal areas), and a single sham session. EEG power spectra were assessed from four 1-min EEG epochs, before, during, and after tDCS. During tDCS the outcome variable, brain rate (fb), changed significantly, and the changes persisted for minutes after tDCS ended. With the DC dipole directed to the left (anode on the left prefrontal area or wrist), fb increased, and with the DC dipole directed to the right (anode on the right prefrontal area or wrist), fb decreased, suggesting asymmetric prefrontal cortex functional organization in the normal human brain. Anodal and cathodal effects were opposite but equally large. Gender left these effects unchanged.

Exploring the N1 Position of Biginelli Compounds: New Insights and Trends for Chemical Diversity Generation of Bioactive Derivatives.

Dihydropyrimidinones (DHPMs) are heterocycles obtained by the multicomponent Biginelli reaction. Recently, new synthetic protocols have allowed us to explore functionalisation at less explored positions of DHPMs, such as the N1 position. In this context, a full literature survey of N1- substituted DHPMs was performed. We analysed 27 papers and identified 379 compounds with substituents at the N1 position, most of them with alkyl groups, and a total of 28% compounds with aromatic substituents attached at the N1 position. N1-substituted DHPMs were explored mainly due to their effects on cancer cell proliferation via numerous targets, such as kinesin Eg5, heat shock protein 70, heat shock protein 90, and the epidermal growth factor receptor. Similarity analyses were performed using the data of 379 DHPMs from different cheminformatic approaches, i.e., chemical property correlations, principal component analysis, similarity networks, and compound clustering.

Cerebral vascular response in airmen exposed to hypobaric hypoxia.

INTRODUCTION: Cerebral vascular response via local and reflex adjustments is part of the integrated response to hypoxia and is coupled with changes in systemic vascular resistances that allow a redistribution of blood flow toward the brain. The cerebral vascular response in airmen exposed to simulated high altitude is not clear, thus we sought to investigate this aspect. METHODS: Four healthy military airmen were exposed to simulated high altitude in a hypobaric chamber according to a standard training protocol. Blood saturation (SpO2) and blood flow velocity with transcranial Doppler from the left middle cerebral artery (Vm) were continuously recorded. Pulsatility Index (PI), resistance index (RI), and systolic/diastolic ratio (S/D ratio) were computed. Alternate hypoxia-hyperoxia trials for 2 and 1 min, respectively, were used to assess the cerebrovascular response. RESULTS: Acute hypoxia induced an increase in Vm that promptly recovered when the oxygen supply was restored (mean increase of 5.5% at 18,000 ft and 17.2% at 25,000 ft). Alternate hypoxia-hyperoxia at 25,000 and 18,000 ft elicited changes in both SpO2 and Vm. In hypoxia, PI significantly decreased (mean decrease o" 25.6% at 18,000 ft and 39.5% at 25,000 ft), as did RI (mean decrease of 18.7% at 18,000 ft and 34.4% at 25,000 ft), while S/D ratio increased. DISCUSSION: The standard altitude training protocol induced a transient cerebrovascular response. The response was as expected, with hypoxia-induced vasodilation and opposite changes when breathing pure oxygen.

Clinical and Electroencephalography Assessment of the Effects of Brivaracetam in the Treatment of Drug-Resistant Focal Epilepsy.

INTRODUCTION: Our aim was to evaluate the clinical and electroencephalographic effects of brivaracetam (BRV) in patients with drug-resistant focal epilepsy. BRV is a new antiepileptic drug (AED) with a high affinity for vesicle protein 2A (SV2A) and recently approved as adjunctive therapy for focal onset seizures. METHODS: In this observational study of six-month duration, BRV (50-200 mg) was administered to 76 patients with drug-resistant focal epilepsy, who were ≥16-year-old and who suffered from daily, weekly, monthly and yearly recurrent seizures. At baseline and after six months of follow-up, we performed a neurological visit, neuropsychological tests: Quality of life in epilepsy-31 (QOLIE31), Epworth Sleepiness Scale (ESS), Intrapersonal Emotional Quotient (IEQ) and an electroencephalogram (EEG; inspective and quantitative analysis). Twenty-four patients underwent an overnight switch from levetiracetam (LEV) to BRV. RESULTS: Seizure frequency of the 54 patients remaining at six months was reduced >50% in 29.6% of cases (responders), <50% in 31.5% (non-responders 1), while it remained unchanged in 38.8% (non-responders 2). Twenty-nine percent of patients early discontinued BRV because of lack of efficacy or minor adverse effects (AEs) like irritability, asthenia or headache. Neuropsychological tests in 28 patients demonstrated a significant improvement in I-EPI scores (p=0.04). Comparable results have been found in the subgroup of patients who switched from LEV to BRV. The EEG quantitative analysis showed a significant reduction of alpha absolute power at six months (p=0.03). Theta band power resulted significantly superior in non-responders than in responders (p=0.03). Furthermore, the δ+θ/α+ß index resulted more elevated in patients with AEs than in patients without. CONCLUSIONS: BRV showed discrete results in terms of efficacy, safety and tolerability, with a good behavioural profile. BRV reduces the power of the alpha band, in correlation with its sedative effects but not with its minor efficacy. Furthermore, the increase in theta band power can be considered as a predictor of scarce response to treatment, while an increase in the δ+θ/α+ß index could be a possible predictor of AEs occurrence.

Neurological, psychological, and cognitive disorders in patients with chronic kidney disease on conservative and replacement therapy.

Chronic kidney disease (CKD) is a highly prevalent condition in the world. Neurological, psychological, and cognitive disorders, related to CKD, could contribute to the morbidity, mortality, and poor quality of life of these patients. The aim of this study was to assess the neurological, psychological, and cognitive imbalance in patients with CKD on conservative and replacement therapy.Seventy-four clinically stable patients affected by CKD on conservative therapy, replacement therapy (hemodialysis (HD), peritoneal dialysis (PD)), or with kidney transplantation (KT) and 25 healthy controls (HC), matched for age and sex were enrolled. Clinical, laboratory, and instrumental examinations, as renal function, inflammation and mineral metabolism indexes, electroencephalogram (EEG), psychological (MMPI-2, Sat P), and cognitive tests (neuropsychological tests, NPZ5) were carried out.The results showed a significant differences in the absolute and relative power of delta band and relative power of theta band of EEG (P = 0.008, P < 0.001, P = 0.051), a positive correlation between relative power of delta band and C-reactive protein (CRP) (P < 0.001) and a negative correlation between estimated glomerular filtration rate (eGFR) (P < 0.001) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) (P < 0.001), in all the samples. Qualitative analysis of EEG showed alterations of Grade 2 (according to Parsons-Smith classification) in patients on conservative therapy, and Grade 2-3 in KT patients. The scales of MMPI-2 hysteria and paranoia, are significantly correlated with creatinine, eGFR, serum nitrogen, CRP, 1,25-(OH)2D3, intact parathyroid hormone (iPTH), phosphorus, and cynical and hysterical personality, are correlated with higher relative power of delta (P = 0.016) and theta band (P = 0.016). Moreover, all NPZ5 scores showed a significant difference between the means of nephropathic patients and the means of the HC, and a positive correlation with eGFR, serum nitrogen, CRP, iPTH, and vitamin D.In CKD patients, simple and noninvasive instruments, as EEG, and cognitive-psychological tests, should be performed and careful and constant monitoring of renal risk factors, probably involved in neuropsychological complications (inflammation, disorders of mineral metabolism, electrolyte disorders, etc.), should be carried out. Early identification and adequate therapy of neuropsychological, and cognitive disorders, might enable a better quality of life and a major compliance with a probable reduction in the healthcare costs.