Showing papers by "David C. Reutens published in 2011"

Language skills of school-aged children prenatally exposed to antiepileptic drugs.

Abstract: OBJECTIVES: Fetal exposure to some antiepileptic drugs (AEDs) carries increased risk of major birth defects, and may be associated with reduced intellectual abilities. The impact on language remains unclear. This study aimed to investigate the impact of fetal AED exposure on language skills. METHODS: Women with epilepsy and their children were recruited to this observational study through the Australian Pregnancy Register for Women with Epilepsy and Allied Disorders. Language skills of 102 AED-exposed children were assessed using the Clinical Evaluation of Language Fundamentals, fourth edition (CELF-4). Assessments were conducted blind to drug. Maternal epilepsy, pregnancy, and medical histories were obtained from prospectively collected records. RESULTS: Mean CELF-4 Core Language scores of children exposed to sodium valproate in monotherapy (mean 91.5, SD 17.5) or polytherapy (mean 73.4, SD = 22.3) were significantly below the standardized test mean of 100 (p < 0.05). Mean language scores of children exposed to carbamazepine or lamotrigine monotherapy, or polytherapy without sodium valproate, were not significantly different from normal. First-trimester sodium valproate dose was negatively correlated with language scores, and significantly predicted language scores after controlling for other group differences. CONCLUSIONS: Fetal exposure to sodium valproate increases the risk of language impairment. This should be taken into account when making treatment decisions for women with epilepsy of childbearing age.

The Australian brain and cognition and antiepileptic drugs study: IQ in school-aged children exposed to sodium valproate and polytherapy.

Abstract: Prenatal exposure to sodium valproate (VPA) and polytherapy has been linked with increased risk of birth defects and cognitive impairment in young children. We evaluated the cognitive impact of prenatal exposure to VPA and polytherapy in school-aged children. Fifty-seven children exposed to VPA (n = 23), polytherapy with VPA (n = 15), or polytherapy without VPA (n = 19) were assessed using the Wechsler Intelligence Scale for Children—Fourth Edition. Information on maternal epilepsy, pregnancy, and medical history was obtained prospectively through the Australian Pregnancy Register for Women with Epilepsy and Allied Disorders. All groups had elevated frequencies of Extremely Low (<70) or Borderline (70–79) Full-Scale IQ (15.8–40.0%). Verbal Comprehension and Working Memory scores in all groups fell significantly below the standardized test mean, while Perceptual Reasoning and Processing Speed scores were relatively intact. Multivariate analysis of covariance analysis revealed significant main effects of VPA on Verbal Comprehension and Working Memory, and of polytherapy on Verbal Comprehension and Processing Speed. Our results suggest that VPA has a dose-dependent negative impact on verbal intellectual abilities, and may also affect working memory. The possibility that inclusion of VPA in many polytherapy regimens may underlie reduced mean scores of polytherapy-exposed children is discussed. (JINS, 2011, 17, 000–000)

Size and Shape of the Corpus Callosum in Adult Niemann-Pick Type C Reflects State and Trait Illness Variables

Abstract: BACKGROUND AND PURPOSE: Variable alterations to the structure of the corpus callosum have been described in adults with NPC, a neurometabolic disorder known to result in both white and gray matter pathology. This study sought to examine the structure of the callosum in a group of adult patients with NPC and compared callosal structure with a group of matched controls, and to relate callosal structure with state and trait illness variables. MATERIALS AND METHODS: Nine adult patients with NPC were matched to control subjects (n = 26) on age and sex. The corpus callosum was segmented from the midsagittal section of T1-weighted images on all subjects, and total area, length, bending angle, and mean thickness were calculated. In addition, 39 regional thickness measures were derived by using a previously published method. All measures were compared between groups, and analyzed alongside symptom measures, biochemical parameters, and ocular-motor measures. RESULTS: The callosal area and mean thickness were significantly reduced in the patient group, and regional thickness differences were greatest in the genu, posterior body, isthmus, and anterior splenium. Global callosal measures correlated significantly with duration of illness and symptom score, and at trend level with degree of filipin staining. Measures of reflexive saccadic peak velocity and gain, and self-paced saccades, correlated strongly with total callosal area. CONCLUSIONS: Callosal structure and size reflect both state and trait markers in adult NPC, and they may be useful biomarkers to index both white and gray matter changes that reflect illness severity and progression.

ORIGINAL RESEARCH Size and Shape of the Corpus Callosum in Adult Niemann-Pick Type C Reflects State and Trait Illness Variables

Abstract: BACKGROUND AND PURPOSE: Variable alterations to the structure of the corpus callosum have been described in adults with NPC, a neurometabolic disorder known to result in both white and gray matter pathology. This study sought to examine the structure of the callosum in a group of adult patients with NPC and compared callosal structure with a group of matched controls, and to relate callosal structure with state and trait illness variables. MATERIALS AND METHODS: Nine adult patients with NPC were matched to control subjects (n 26) on age and sex. The corpus callosum was segmented from the midsagittal section of T1-weighted images on all subjects, and total area, length, bending angle, and mean thickness were calculated. In addition, 39 regional thickness measures were derived by using a previously published method. All measures were compared between groups, and analyzed alongside symptom measures, biochemical parameters, and ocular-motor measures. RESULTS: The callosal area and mean thickness were significantly reduced in the patient group, and regional thickness differences were greatest in the genu, posterior body, isthmus, and anterior splenium. Global callosal measures correlated significantly with duration of illness and symptom score, and at trend level with degree of filipin staining. Measures of reflexive saccadic peak velocity and gain, and self-paced saccades, correlated strongly with total callosal area. CONCLUSIONS: Callosal structure and size reflect both state and trait markers in adult NPC, and they may be useful biomarkers to index both white and gray matter changes that reflect illness severity and progression.

Thickness profile generation for the corpus callosum using Laplace's equation

Abstract: The corpus callosum facilitates communication between the cerebral hemispheres. Morphological abnormalities of the corpus callosum have been identified in numerous psychiatric and neurological disorders. To quantitatively analyze the thickness profile of the corpus callosum, we adapted an automatic thickness measurement method, which was originally used on magnetic resonance (MR) images of the cerebral cortex (Hutton et al. [2008]: NeuroImage 40:1701–10; Jones et al. [2002]: Hum Brain Mapp 11:12–32; Schmitt and Bohme [2002]: NeuroImage 16:1103–9; Yezzi and Prince [2003]: IEEE Trans Med Imaging 22:1332–9), to MR images of the corpus callosum. The thickness model was derived by computing a solution to Laplace's equation evaluated on callosal voxels. The streamlines from this solution form non-overlapping, cross-sectional contours the lengths of which are modeled as the callosal thickness. Apart from the semi-automated segmentation and endpoint selection procedures, the method is fully automated, robust, and reproducible. We compared the Laplace method with the orthogonal projection technique previously published (Walterfang et al. [2009a]: Psych Res Neuroimaging 173:77–82; Walterfang et al. [2008a]: Br J Psychiatry 192:429–34; Walterfang et al. [2008b]: Schizophr Res 103:1–10) on a cohort of 296 subjects, composed of 86 patients with chronic schizophrenia (CSZ), 110 individuals with first-episode psychosis, 100 individuals at ultra-high risk for psychosis (UHR; 27 of whom later developed psychosis, UHR-P, and 73 who did not, UHR-NP), and 55 control subjects (CTL). We report similar patterns of statistically significant differences in regional callosal thickness with respect to the comparisons CSZ vs. CTL, UHR vs. CTL, UHR-P vs. UHR-NP, and UHR vs. CTL. Hum Brain Mapp, 2011. © 2011 Wiley Periodicals, Inc.

A randomized, double‐blind, placebo‐controlled trial of levetiracetam for dyskinesia in Parkinson's disease

Abstract: Background: This randomized double blind, placebo-controlled crossover study investigated the antidyskinetic effects of levetiracetam in Parkinson's disease. Methods:Sixteen participants with levodopa-induced dyskinesia were enrolled. Hourly videotaped dyskinesia assessments scored by the Goetz method and hourly Unified Parkinson's Disease Rating Scale motor subscale scoring were conducted on 1 day at the end of each treatment period. Results: Dyskinesia was slightly less on placebo (P = .26). Patient diary records also showed less dyskinesia on placebo (P = .10). Parkinsonism was a little worse on levetiracetam, at borderline statistical significance (P = .05).Conclusions: Levetiracetam was well tolerated at doses up to 2000 mg per day, but we did not detect any antidyskinetic properties.

The relationship between mood disorders and MRI findings following traumatic brain injury.

Abstract: Background: High rates of depression have been reported in individuals with traumatic brain injury (TBI). The purpose of the current study was to investigate the relationship between structural MRI findings and the development of novel cases of post-injury depression in this populationMethods: The study has a cross-sectional design. Assessments were conducted on average 2.2 years post-injury. Participants were 54 individuals (76% male, mean age 35 years, median PTA duration 16 days) who had sustained a TBI. Depression was assessed with the Structured Clinical Interview for DSM-IV (SCID-IV). Structural MRI scans were performed with a 1.5 Tesla machine.Results: The presence of lesions in the frontal, temporal, parietal and the sublobar regions was not related to depression. However, an imbalance of left vs right frontal and parietal viable brain volumes was related to the development of depression.Discussion: These findings are in support of Heller's model of emotion processing, but should be replicated usi...

Morphology-based interslice interpolation using local intensity information for segmentation

Abstract: The interpolation of contours between slices in the absence of the original intensity image has been a challenging task and investigated for many years. In some applications of medical imaging, however, objects of interest are segmented manually on selected slices and the intensity image is available. The latter can be used to improve the quality of interpolated segmentations. In this paper, we present a two-step approach to accurate interslice interpolation of manual segmentations using information from both object shape and image intensity. Morphology based shape interpolation followed by the application of intensity-based neighborhood voting to adjust boundary voxels were used to integrate the two information sources. We compared our method to three existing interpolation methods for magnetic resonance images of mouse and human brain. The proposed method outperformed the three methods, having lower average error rates.

Synthesis and Structural Characterization of (Z)-3-[(4-Chlorophenylamino) Methylene] Naphthalene-2(3H)-One: An Enol, Keto or Zwitterionic Tautomer?

Abstract: The structure of the title compound was determined using X-ray crystallography at both 173 and 293 K. The molecular structure and packing did not change significantly with temperature and a disordered structure was identified comprising a keto and enol tautomeric form. Analysis of the bond lengths in the vicinity of the C=O group suggested the keto form was predominantly in its zwitterionic form structure. 1H NMR spectroscopy showed the presence of a single compound in solution with two diagnostic doublets demonstrating the compound had an NH group next to a CH group resembling the zwitterionic form of the compound.

MRI demodulation frequency changes provide different information

Abstract: Uecker and coworkers claim that our conclusion in Ref. 1 was supported by neither the theoretical arguments nor the experimental data presented. They purport that image improvements were due to an incorrect restoration of the low-resolution signal as a consequence of the interpolation method used, and high-frequency noise causes an illusion of resolution enhancement. We used the zero-filling approach to implement sinc interpolation (2), which is identical to their method. We tested our method with and without the addition of noise, and showed that improvements were present in both cases (see Figs. 4 and 5 in Ref. 1). Therefore, image enhancement was not an illusion caused by high-frequency noise components. Furthermore, comparison of Fig. 4(a) to (b) in Ref. 1 shows that enhancement is most observable at object features, where dimensions are near the effective width of the point spread function (PSF). We conducted a point source simulation to explain why image shifts provide different information to sinc interpolation. According to sampling theory, if a continuous signal is sampled at the Nyquist rate, then it can be recovered exactly using the sinc function over an infinite number of sample points (3). In practice, however, sampling is finite. Therefore, we considered a finite number of samples and different sampling locations with respect to point source location. In Fig. 1, a point source is represented as a sinc function, corresponding to the shape of the PSF. The solid line represents the real data, sampled according to the Nyquist rate at locations of circles. The dot-dashed line is the interpolation obtained by zero-filling of the Fourier transform of the discrete samples. We are interested in the magnitude of the main lobe of the interpolated data, because it defines point source strength. We ignore side lobes, as they contribute to image background noise. Figure 1 shows that, when point source and sampling location misalign, the interpolated main lobe peak is smaller than that of the solid line. Here, we found the ratio between the height of the peak of the interpolated and solid curves, when the point source is at a half distance between sampling points, to be 0.92, 0.96, and 0.97 for 10, 20, and 30 samples, respectively. Therefore, the difference reduces as a number of samples increase. Figure 2 depicts two point sources, one aligned with a sampling point and another shifted by two and a half distances between sampling points. The result shows that

A Rapid Procedure for Spectral Similarity Matching of Heteronuclear Single Quantum Coherence Spectra

Abstract: A new peak-based quantitative spectra matching method using affinity matrix spectral analysis is proposed. An affinity matrix is generated to describe similarity between 2D HSQC peaks given their spatial location. Application of the approach gives best matched peaks of two different spectra with the same or different number of peaks. Results were validated against a previously published method. The new algorithm was found to be an order of magnitude faster in finding matched peaks, in comparison to our previously reported technique. This speed-up allows large number of peaks to be matched quickly, meaning that structures of high complexity can be compared across large structure databases. Matching examples are provided for 15N HSQC spectra of protein samples, which we use to establish performance.

Synthesis and X-Ray Crystal Structure of 1- and 2-Cinnamoyaloxy Acetonaphthones

Abstract: The synthesis of titled compounds were achieved in one step using hydroxyl naphthones and substituted cinnamic acids in the presence of a catalytic amount of phosphorus oxychloride. X-ray crystal studies were undertaken for three compounds and the results are presented. Compounds 1 (C22H15F3O3) and 3 (C21H15BrO3) formed a monoclinic crystals while compound 2 (C22H15F3O3) formed a triclinic crystals. The observed space group of these compounds is P21/c and P $$ \bar{1} $$ respectively. The 2-substituted compounds showed identical space group and showed a perpendicular arrangements of each of the substituents to the plane of the naphthyl ring. On the contrary, the 1-substituted cinnamoyal compound showed an orthogonal arrangement to naphthyl ring but the acetyl group was almost planar relative to the naphthyl moiety. The characterization of the structures of the compounds was also accomplished using high-resolution NMR spectroscopic techniques. The synthesis of titled compound was achieved in one step using hydroxyl naphthones and substituted cinnamic acids in the presence of a catalytic amount of phosphorus oxychloride. X-ray crystal studies were undertaken for three compounds and the results are presented. Compounds 1 and 3 formed a monoclinic crystal while compound 2 formed a triclinic crystal. The molecular formulae of compounds are as follows: C22H15F3O3 (1 and 2) and C21H15BrO3(3) . The observed space group of these compounds is P21/c and P1 respectively.

Synthesis and Characterization of Oxazolopyridine and Benzoxazole Derivatives.

Abstract: Synthesis of piperazinyl-substituted oxazolopyridine and benzoxazole was achieved in three steps starting from aminophenol and carbon disulfide. Condensation of aminophenols with carbon disulfide in ethanol using potassium hydroxide as catalyst gave the required benzoxazole thiol in one step. Treatment of the thiol with piperazine and substituted piperazine derivatives in toluene furnished the titled compounds in good yield. We introduced halogen substitution in the pendant arm of the piperazine derivatives for versatile functionalization. We report the synthesis and characterization of these compounds using high resolution NMR techniques.