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Global metabolomic profiling offers novel opportunities for the discovery of biomarkers and for the elucidation of pathogenic mechanisms that might lead to the development of novel therapies. GLUT1 deficiency syndrome (GLUT1-DS) is an inborn error of metabolism due to reduced function of glucose transporter type 1. Clinical presentation of GLUT1-DS is heterogeneous and the disorder mirrors patients with epilepsy, movement disorders, or any paroxysmal events or unexplained neurological manifestation triggered by exercise or fasting. The diagnostic biochemical hallmark of the disease is a reduced cerebrospinal fluid (CSF)/blood glucose ratio and the only available treatment is ketogenic diet. This study aimed at advancing our understanding of the biochemical perturbations in GLUT1-DS pathogenesis through biochemical phenotyping and the treatment of GLUT1-DS with a ketogenic diet. Metabolomic analysis of three CSF samples from GLUT1-DS patients not on ketogenic diet was feasible inasmuch as CSF sampling was used for diagnosis before to start with ketogenic diet. The analysis of plasma and urine samples obtained from GLUT1-DS patients treated with a ketogenic diet showed alterations in lipid and amino acid profiles. While subtle, these were consistent findings across the patients with GLUT1-DS on ketogenic diet, suggesting impacts on mitochondrial physiology. Moreover, low levels of free carnitine were present suggesting its consumption in GLUT1-DS on ketogenic diet. 3-hydroxybutyrate, 3-hydroxybutyrylcarnitine, 3-methyladipate, and N-acetylglycine were identified as potential biomarkers of GLUT1-DS on ketogenic diet. This is the first study to identify CSF, plasma, and urine metabolites associated with GLUT1-DS, as well as biochemical changes impacted by a ketogenic diet. Potential biomarkers and metabolic insights deserve further investigation.

We analyzed by next-generation sequencing (NGS) 67 epilepsy genes in 19 patients with different types of either isolated or syndromic epileptic disorders and in 15 controls to investigate whether a quick and cheap molecular diagnosis could be provided. The average number of nonsynonymous and splice site mutations per subject was similar in the two cohorts indicating that, even with relatively small targeted platforms, finding the disease gene is not an univocal process. Our diagnostic yield was 47% with nine cases in which we identified a very likely causative mutation. In most of them no interpretation would have been possible in absence of detailed phenotype and familial information. Seven out of 19 patients had a phenotype suggesting the involvement of a specific gene. Disease-causing mutations were found in six of these cases. Among the remaining patients, we could find a probably causative mutation only in three. None of the genes affected in the latter cases had been suspected a priori. Our protocol requires 8-10 weeks including the investigation of the parents with a cost per patient comparable to sequencing of 1-2 medium-to-large-sized genes by conventional techniques. The platform we used, although providing much less information than whole-exome or whole-genome sequencing, has the advantage that can also be run on 'benchtop' sequencers combining rapid turnaround times with higher manageability.

Background and Purpose: Several techniques, including chymopapain, mechanical aspiration, laser-based disk decompression, and endoscopic keyhole surgery, have been proposed as minimally invasive alternatives to fusion for treating cervical disk herniation, though none has gained wide acceptance. The purpose of this study was to assess feasibility, safety, and preliminary clinical results of percutaneous plasma-mediated radio-frequency-based diskectomy for cervical disk herniation., Methods: Patients (N = 55) with cervical soft disk protrusion were treated over a 29-month period. They had radicular pain; 3 patients also had moderate myelopathy. The procedure was performed with the Perc-DC SpineWand by using an anterior approach. Most cases were conducted with local anesthetic on an outpatient basis. Clinical outcomes were graded by using the Macnab criteria., Results: At 2 months, outcomes were good or excellent in 44/55 (80%) patients; the success rate was similar at 6 months, when 44 (85%) patients (n = 52/55) had good or excellent results. One clinically relevant complication (infectious diskitis) occurred within the first month postprocedure and was successfully treated. One technical complication (in situ rupture of the device tip) was observed; however, the patient remained asymptomatic during the 2-year follow-up. The 3 patients with clinical myelopathy experienced regression of cord compression symptoms; MR imaging in 2 patients showed morphologic evidence of reduction of cord compression., Conclusions: Plasma radio-frequency-based diskectomy in the cervical spine appears to be a minimally invasive low-risk approach, which is easy to perform, associated with only minimal discomfort to the patient, and effective in the short term.