Spectroscopic detection of brain propylene glycol in neonates: Effects of different pharmaceutical formulations of phenobarbital

Background The first choice for treatment of neonatal convulsions is intravenous phenobarbital, which contains propylene glycol (PG) as a solvent. Although PG is generally considered safe, the dosage can exceed safety thresholds in neonates. High PG levels can cause lactic acidosis. Purpose/Hypothesis To investigate a relationship between brain PG concentration and medication administered to neonates, and to study if a correlation between spectroscopically detected PG and lactate was present. Study Type Retrospective. Population Forty‐one neonates who underwent MRI/MRS. Field Strength/Sequence Short echo time single voxel MRS at 1.5T. Assessment Spectra were quantified. Concentrations of PG were correlated with medication administered, because intravenously administered phenobarbital solutions contained 10, 25, or 50 mg phenobarbital per ml, all containing 350 mg PG per ml. The interval between medication and MRI/MRS was determined. Statistical Tests Chi‐square test, Student's t‐test, Mann–Whitney U‐test and Spearman correlation. Results Eighteen neonates had brain PG >1 mM (median 3.4 mM, maximum 9.5 mM). All 18 neonates with high brain PG and 14 neonates with low brain PG (<1 mM) received phenobarbital as the only source of PG. Nine neonates did not receive any phenobarbital/PG‐containing medication. Neonates with high brain PG more often received 10 mg/ml phenobarbital, resulting in higher PG dose (high vs. low brain PG (median [interquartile range]: 1400 [595] vs. 350 [595] mg/kg, respectively, P < 0.01). In addition, the interval between the last phenobarbital dose and MRI was shorter in the high brain PG group (high vs. low brain PG: 16 [21] vs. 95 [83] hours, respectively, P < 0.001). Within neonates that received phenobarbital, there was no conclusive correlation between spectroscopically detected PG and lactate (Spearman's rho = 0.23, P = 0.10). Data Conclusion These MRS findings may increase awareness of potentially toxic PG concentrations in the neonatal brain due to intravenous phenobarbital administration and its dependence on the phenobarbital formulation used. Level of Evidence:4Technical Efficacy:Stage

Relevance of neuroimaging for neurocognitive and behavioral outcome after pediatric traumatic brain injury

This study aims to (1) investigate the neuropathology of mild to severe pediatric TBI and (2) elucidate the predictive value of conventional and innovative neuroimaging for functional outcome. Children aged 8–14 years with trauma control (TC) injury (n = 27) were compared to children with mild TBI and risk factors for complicated TBI (mildRF+, n = 20) or moderate/severe TBI (n = 17) at 2.8 years post-injury. Neuroimaging measures included: acute computed tomography (CT), volumetric analysis on post-acute conventional T1-weighted magnetic resonance imaging (MRI) and post-acute diffusion tensor imaging (DTI, analyzed using tract-based spatial statistics and voxel-wise regression). Functional outcome was measured using Common Data Elements for neurocognitive and behavioral functioning. The results show that intracranial pathology on acute CT-scans was more prevalent after moderate/severe TBI (65%) than after mildRF+ TBI (35%; p = .035), while both groups had decreased white matter volume on conventional MRI (ps ≤ .029, ds ≥ −0.74). The moderate/severe TBI group further showed decreased fractional anisotropy (FA) in a widespread cluster affecting all white matter tracts, in which regional associations with neurocognitive functioning were observed (FSIQ, Digit Span and RAVLT Encoding) that consistently involved the corpus callosum. FA had superior predictive value for functional outcome (i.e. intelligence, attention and working memory, encoding in verbal memory and internalizing problems) relative to acute CT-scanning (i.e. internalizing problems) and conventional MRI (no predictive value). We conclude that children with mildRF+ TBI and moderate/severe TBI are at risk of persistent white matter abnormality. Furthermore, DTI has superior predictive value for neurocognitive out-come relative to conventional neuroimaging

Twelve week liraglutide or sitagliptin does not affect hepatic fat in type 2 diabetes: a randomised placebo-controlled trial

_Aims/hypothesis:_ Glucagon-like peptide (GLP)-1-based therapies have been suggested to improve hepatic steatosis. We assessed the effects of the GLP-1 receptor agonist liraglutide and the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin on hepatic steatosis and fibrosis in patients with type 2 diabetes. _Methods:_ In this 12 week, parallel, randomised, placebo-controlled trial, performed at the VU University Medical Center between July 2013 and August 2015, 52 overweight patients with type 2 diabetes treated with metformin and/or sulphonylurea agent ([mean ± SD] age 62.7 ± 6.9 years, HbA1c 7.3 ± 0.7% or 56 ± 1 mmol/mol) were allocated to once daily liraglutide 1.8 mg (n = 17), sitagliptin 100 mg (n = 18) or matching placebos (n = 1

Joint assessment of white matter integrity, cortical and subcortical atrophy to distinguish AD from behavioral variant FTD: A two-center study

We investigated the ability of cortical and subcortical gray matter (GM) atrophy in combination with white matter (WM) integrity to distinguish behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD) and from controls using voxel-based morphometry, subcortical structure segmentation, and tract-based spatial statistics. To determine which combination of MR markers differentiated the three groups with the highest accuracy, we conducted discriminant function analyses. Adjusted for age, sex and center, both types of dementia had more GM atrophy, lower fractional anisotropy (FA) and higher mean (MD), axial (L1) and radial diffusivity (L23) values than controls. BvFTD patients had more GM atrophy in orbitofrontal and inferior frontal areas than AD patients. In addition, caudate nucleus and nucleus accumbens were smaller in bvFTD than in AD. FA values were lower; MD, L1 and L23 values were higher, especially in frontal areas of the brain for bvFTD compared to AD patients. The combination of cortical GM, hippocampal volume and WM integrity measurements, classified 97-100% of controls, 81-100% of AD and 67-75% of bvFTD patients correctly. Our results suggest that WM integrity measures add complementary information to measures of GM atrophy, thereby improving the classification between AD and bvFTD

Localisation of the central sulcus region in glioma patients with three-dimensional fluid-attenuated inversion recovery and volume rendering: comparison with functional and conventional magnetic resonance

Purpose. Volume rendering (VR) of three-dimensional (3D) fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) images shows regional intensity differences, reflecting the central sulcus (CS) region and occipital cortex. The purpose of this study was to determine whether 3D FLAIR with VR could be used as an alternative method to localise the CS region in comparison with functional and conventional MR-imaging in patients with perirolandic glioma. Methods. Eleven patients with intracranial gliomas were studied with single-slab 3D FLAIR including VR and conventional T1-weighted imaging. In all patients, preoperative functional magnetic resonance imaging (fMRI) was performed with a motor paradigm of the hand. The hypo-intense central gyri on 3D FLAIR with VR were interpreted as the CS area. Localisation of the motor hand knob on anatomical images and fMRI results were used for identification of the primary motor cortex. Results. Anatomical localisation of the motor hand knob on T1-weighted images was possible in 91% of both hemispheres. In 73% of the affected hemispheres (AH) and 91% of the unaffected hemispheres (UH) the hand knob and CS region could be identified on 3D FLAIR axial and VR images, respectively. With one exception, fMRI activation confirmed the CS region as observed with 3D FLAIR with VR. Conclusions. Volume rendering of 3D FLAIR MR images shows central hypo-intensities frequently corresponding with the CS region. Two-dimensional localisation of the CS region on conventional T1-weighted images and fMRI seems favourable compared to 3D FLAIR. However, in selected cases, especially where fMRI is not possible or feasible, volume rendering with 3D FLAIR may enhance the 3D visualisation of gliomas in relation to the CS region which can be used as an alternative method in the presurgical structural and functional evaluation of neurosurgical patient

Cerebral proton magnetic resonance spectroscopy of a patient with giant axonal neuropathy

Magnetic resonance imaging of a girl with giant axonal neuropathy revealed a progressive white matter disease. In close agreement with histopathological features reported previously, localized proton magnetic resonance spectroscopy at 9 and 12 years of age indicated a specific damage or loss of axons (reduced N-acetylaspartate and N-acetylaspartylglutamate) accompanied by acute demyelination (elevated choline-containing compounds, myo-inositol, and lactate) in white matter as well as a generalized proliferation of glial cells (elevated choline-containing compounds and myo-inositol) in both gray and white matter. (C) 2002 Elsevier Science B.V. All rights reserved