Luigi Barberini

Metabolomics enables the parallel assessment of the levels of a broad range of metabolites and has been shown to have a great impact in investigation of physiological status, diagnosing diseases, measuring the response to treatment, discovering biomarkers, identifying perturbed pathways due to disease or treatment, functional genomics. Common analytical techniques applied to metabolomics are nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. The most commonly used biological samples for metabolomics studies are urine, blood plasma or serum. Because of its characteristics and simple non-invasive methods of collection, urine is particularly suited for metabolomic analysis even in small babies. The use of non-invasive techniques is an essential requirement in neonatal medicine, especially in very preterm infants. Little is known about the overall metabolic status of the term and preterm neonate, but it can be currently assessed by metabolomic analysis of urine. Other important applications of metabolomic analysis of urine in the newborn could be the monitoring of postnatal metabolic maturation over time, the identification of biomarkers as early predictors of outcome, and the implementation and monitoring of a tailored management of neonatal disorders. The clinical management of neonates could be probably improved if more information about perinatal and neonatal maturation processes and their metabolic background were available. The metabolomics approach, together with transcriptomics and proteomics, will have substantial impact on development of diagnostics, therapeutics and drug development and may be an important new tool in neonatology.

Summary: Purpose: To describe the correlations between spiking pattern and EEG power spectrum frequency in DBA/2J mice, a model for murine absence seizures, after γ-aminobutyric acid (GABA)B modulation.Methods: The animals were first tested with the GABAB agonist l-baclofen followed by the GABAB antagonist SCH 50911. Moreover, digital EEGs recorded under experimental conditions were processed at baseline and 10 and 20 min after l-baclofen injection. This procedure was followed by injection of the GABAB antagonist SCH50911 and by an additional EEG evaluation at 10 and 20 min from drug administration. The power spectra analysis of signals was obtained for delta (0.5–3 Hz), theta (3.5–7.5 Hz), alpha (8–12 Hz), beta (13–20 Hz), and gamma (21–50 Hz) frequencies.Results: The spiking pattern and power spectrum of beta activity was increased by ≤80% after administration of 5 mg/kg l-baclofen, whereas gamma power frequency decreased to the same extent. After administration of 50 mg/kg SCH 50911, spiking activity and beta power frequencies were markedly reduced (>80%), whereas gamma power increased (correlation, 0.92; p < 0.001). The remaining frequency bands were unaffected.Conclusions: This study confirms the potential of GABAB antagonists in contrasting seizure absence in rodent models and suggests the application of drugs with a similar mechanism in humans. In addition, because GABAB antagonists not only contrast seizure in rodent models of absence but also improve “cognitive” performance, it could be hypothesized that gamma increase, correlated with optimized cortical binding during coherent percepts, may produce potential cognition-enhancing effects.

The objective of this study was to study genetic and phenotypic features of a family with X-linked Charcot-Marie-Tooth consisting of a healthy father, affected mother, two affected sons and one healthy one. A detailed electrophysiological and neuroimaging study, along with sequencing of the Cx32 gene, was performed in all family members. A novel Cx32 123 G>C mutation, determining an aminoacid variation (Glu41Asp), was found in the mother and the affected sons. An alteration in brainstem evoked potentials was found in the mother and one affected son. The affected son, who underwent magnetic resonance imaging, showed symmetrical hyperintensities in paratrigonal white matter, not found in his heterozygous mother, while both subjects exhibited alterations in brain metabolite ratios derived from localised proton-magnetic resonance spectroscopy. These data extend previous findings about central nervous system involvement in Cx32 mutated subjects and further support a functional role of the protein expression in oligodendrocytes.

Mirror focus (MF) is a cortical epileptogenic lesion that is posited to develop in the contralateral site to a cortical primary focus (PF) by secondary epileptogenic mechanisms. Previous animal evidence supports the implication of gamma-aminobutyric acid (GABA) in this phenomenon, but this contention has not yet been substantiated by clinical findings. Here we report for the first time clinical evidence suggesting the involvement of GABAergic cortical transmission in MF pathogenesis, in a 37-year-old man affected by a lesional PF in the right frontal lobe and a homotopic MF in the contralateral hemisphere, triggered by hyperventilation. One year after surgical excision of the PF, the electric activity of the MF remained unchanged, but was accompanied by a significant increase in the density of GABA(A)/benzodiazepine receptor binding in the left frontal lobe, as measured by (123)I-Iomazenil SPECT. These results extend previous evidence on the involvement of GABAergic signaling in MF pathophysiology.

Vagus nerve stimulation (VNS), an adjunctive approach for the treatment of epilepsy, was performed in three multiple sclerosis (MS) patients displaying postural cerebellar tremor (PCT) and dysphagia. Following VNS, improvement of PCT and dysphagia was manifested over a period of two and three months, respectively. In view of the involvement of the main brainstem visceral component of the vagus, the nucleus tractus solitarius (NTS), in modulating central pattern generators (CPGs) linked to both olive complex pathway and swallowing, improvement is likely to be VNS related. The results obtained suggest an additional therapeutic application for VNS and may represent a novel form of treatment in patients with severe MS.