Measuring impulsivity in Parkinson's disease: a correlational and structural neuroimaging study using different tests.

BACKGROUND AND PURPOSE: Impulsivity is an aspect of personality and a major component of multiple neuropsychiatric conditions. In Parkinson's disease, it has been associated with the expression of impulse control disorders, a highly prevalent non-motor complication. Even though multiple tests of impulsivity have been used in this context, the impact of test choice has not been addressed. The aim was to evaluate whether different impulsivity measures in Parkinson's disease share substantial inter-scale and anatomical correlations or rather mirror different underlying phenomena. METHODS: In a consecutive sample of 89 Parkinson's disease patients without impulse control disorders, four common tests were evaluated assessing different aspects of impulsivity: impulsiveness trait, decisions under implicit risk with and without losses, and delay discounting. Correlations among test scores were analysed and each score was used as a regressor in a set of grey matter volume (GMV) voxel-based morphometry analyses to explore their brain structural correlates. RESULTS: No significant correlations were found between the different impulsivity tests. Furthermore, their structural brain correlates were divergent. Impulsiveness trait appeared to be associated with lower GMV in dorsal-lateral prefrontal cortices, implicit risk (with losses) with higher GMV in the left nucleus accumbens and lower left insular GMV, implicit risk (without losses) with higher GMV in the left lingual gyrus and lower GMV in the gyri recti and delay discounting with higher GMV in the left nucleus accumbens. CONCLUSIONS: In Parkinson's disease, different impulsivity measures reflect very dissimilar behavioural and brain structural correlates. Our results suggest that parkinsonian impulsivity is not a unitary phenomenon but rather a heterogeneous entity.

Widespread Increased Diffusivity Reveals Early Cortical Degeneration in Huntington Disease.

BACKGROUND AND PURPOSE: Huntington disease is a devastating genetic neurodegenerative disorder for which no effective treatment is yet available. Although progressive striatal atrophy is its pathologic hallmark, concomitant cortical deterioration is assumed to occur, but it is poorly characterized. Our objective was to study the loss of cortical integrity and its association with clinical indicators throughout the course of the disease. MATERIALS AND METHODS: Using a cohort of 39 patients with Huntington disease and 25 controls with available MR imaging (T1WI and DTI), we compared cortical atrophy and intracortical diffusivity across disease stages. Intracortical diffusivity is a DTI-derived metric that has recently been suggested to detect incipient neuronal death because water can diffuse more freely in cortical regions with reduced neural density. RESULTS: We observed progressive thinning and increasing diffusivity within the cerebral cortex of patients with Huntington disease (P < .05, corrected for multiple comparisons). Most important, in the absence of pronounced atrophy, widespread increased diffusivity was already present in individuals with premanifest Huntington disease, correlating, in turn, with clinical and disease-specific progression markers. CONCLUSIONS: Intracortical diffusivity may be more sensitive than cortical thinning for tracking early neurodegeneration in Huntington disease. Moreover, our findings provide further evidence of an early cortical compromise in Huntington disease, which contributes to our understanding of its clinical phenotype and could have important therapeutic implications.

A visual quality control scale for clinical arterial spin labeling images.

BACKGROUND: Image-quality assessment is a fundamental step before clinical evaluation of magnetic resonance images. The aim of this study was to introduce a visual scoring system that provides a quality control standard for arterial spin labeling (ASL) and that can be applied to cerebral blood flow (CBF) maps, as well as to ancillary ASL images. METHODS: The proposed image quality control (QC) system had two components: (1) contrast-based QC (cQC), describing the visual contrast between anatomical structures; and (2) artifact-based QC (aQC), evaluating image quality of the CBF map for the presence of common types of artifacts. Three raters evaluated cQC and aQC for 158 quantitative signal targeting with alternating radiofrequency labelling of arterial regions (QUASAR) ASL scans (CBF, T1 relaxation rate, arterial blood volume, and arterial transient time). Spearman correlation coefficient (r), intraclass correlation coefficients (ICC), and receiver operating characteristic analysis were used. RESULTS: Intra/inter-rater agreement ranged from moderate to excellent; inter-rater ICC was 0.72 for cQC, 0.60 for aQC, and 0.74 for the combined QC (cQC + aQC). Intra-rater ICC was 0.90 for cQC; 0.80 for aQC, and 0.90 for the combined QC. Strong correlations were found between aQC and CBF maps quality (r = 0.75), and between aQC and cQC (r = 0.70). A QC score of 18 was optimal to discriminate between high and low quality clinical scans. CONCLUSIONS: The proposed QC system provided high reproducibility and a reliable threshold for discarding low quality scans. Future research should compare this visual QC system with an automatic QC system.

Bullseye's representation of cerebral white matter hyperintensities.

BACKGROUND AND PURPOSE: Visual rating scales have limited capacities to depict the regional distribution of cerebral white matter hyperintensities (WMH). We present a regional-zonal volumetric analysis alongside a visualization tool to compare and deconstruct visual rating scales. MATERIALS AND METHODS: 3D T1-weighted, T2-weighted spin-echo and FLAIR images were acquired on a 3T system, from 82 elderly participants in a population-based study. Images were automatically segmented for WMH. Lobar boundaries and distance to ventricular surface were used to define white matter regions. Regional-zonal WMH loads were displayed using bullseye plots. Four raters assessed all images applying three scales. Correlations between visual scales and regional WMH as well as inter and intra-rater variability were assessed. A multinomial ordinal regression model was used to predict scores based on regional volumes and global WMH burdens. RESULTS: On average, the bullseye plot depicted a right-left symmetry in the distribution and concentration of damage in the periventricular zone, especially in frontal regions. WMH loads correlated well with the average visual rating scores (e.g. Kendall's tau [Volume, Scheltens]=0.59 CI=[0.53 0.62]). Local correlations allowed comparison of loading patterns between scales and between raters. Regional measurements had more predictive power than global WMH burden (e.g. frontal caps prediction with local features: ICC=0.67 CI=[0.53 0.77], global volume=0.50 CI=[0.32 0.65], intra-rater=0.44 CI=[0.23 0.60]). CONCLUSION: Regional-zonal representation of WMH burden highlights similarities and differences between visual rating scales and raters. The bullseye infographic tool provides a simple visual representation of regional lesion load that can be used for rater calibration and training.

Valor de la PET/TC cerebral con 18F-fluorocolina en la detección de recurrencias de neoplasias primarias del sistema nervioso central / The usefulness of 18F-fluorocholine PET/CT in the detection of recurrence of central nervous system primary neoplasms

Objetivo. Estudiar el impacto clínico en el manejo de los pacientes de la 18F-fluorocolina (18F-COL) en la recurrencia de neoplasias cerebrales primarias. Material y métodos. Se estudió prospectivamente a 21 pacientes con sospecha de recidiva de neoplasia cerebral primaria mediante PET/TC cerebral con 18F-COL en uso compasivo. La distribución por patología de los pacientes estudiados fue: 3 astrocitomas grado II, 3 astrocitomas grado III, un oligodendroglioma grado II, 3 oligodendrogliomas grado iii, un oligoastrocitoma grado iii, 4 glioblastomas multiformes, una gliomatosis cerebri y 5 meningiomas. Se consideraron positivos los estudios en los que había una captación visualmente significativa respecto al fondo del parénquima cerebral. Resultados. Diecisiete de los pacientes fueron positivos, comprobándose dicho resultado por histología (10 de ellos) o seguimiento clínico y por neuroimagen, sin hallarse falsos positivos o negativos. El índice target to backgroud ratio medio para los positivos fue de 8,02 y para los negativos de 0,94, lo que representa una diferencia significativa (p=0,003). Conclusión. La PET/TC con 18F-COL presenta resultados alentadores en la valoración de pacientes con sospecha de recidiva (AU)

Aim. To study the usefulness of 18F-fluorocholine (FCH) in detecting the recurrence of primary brain tumours. Material and methods. A prospective study was conducted on brain PET/CT with FCH for compassionate use in 21 patients with suspected recurrence of a primary brain tumour. The distribution by pathology was: three grade II astrocytomas, three grade III astrocytomas, one grade II oligodendroglioma, three grade III oligodendrogliomas, one grade III oligoastrocytoma, four glioblastoma multiform, one gliomatosis cerebri, and five meningiomas. Studies in which there was a visually significant uptake in the brain parenchyma were classified as positive. Results. A total of 17 patients were classified as positive, with the results being confirmed by histology (10 cases) or clinical follow-up and imaging, with no false positives or negatives. The mean SUVmax for positive patients was 8.02 and 0.94 for the negative ones, which was significantly different (P=.003) Conclusion. PET/CT with FCH shows encouraging results in the evaluation of patients with suspected recurrence of primary brain neoplasms (AU)

The usefulness of 18F-fluorocholine PET/CT in the detection of recurrence of central nervous system primary neoplasms. / Valor de la PET/TC cerebral con 18F-fluorocolina en la detección de recurrencias de neoplasias primarias del sistema nervioso central.

AIM: To study the usefulness of 18F-fluorocholine (FCH) in detecting the recurrence of primary brain tumours. MATERIAL AND METHODS: A prospective study was conducted on brain PET/CT with FCH for compassionate use in 21 patients with suspected recurrence of a primary brain tumour. The distribution by pathology was: three grade ii astrocytomas, three grade iii astrocytomas, one grade ii oligodendroglioma, three grade iii oligodendrogliomas, one grade iii oligoastrocytoma, four glioblastoma multiform, one gliomatosis cerebri, and five meningiomas. Studies in which there was a visually significant uptake in the brain parenchyma were classified as positive. RESULTS: A total of 17 patients were classified as positive, with the results being confirmed by histology (10 cases) or clinical follow-up and imaging, with no false positives or negatives. The mean SUVmax for positive patients was 8.02 and 0.94 for the negative ones, which was significantly different (P=.003) CONCLUSION: PET/CT with FCH shows encouraging results in the evaluation of patients with suspected recurrence of primary brain neoplasms.

Esclerosis concéntrica de Balo: una presentación que simula un ictus isquémico / Balo concentric sclerosis: a presentation mimicking ischaemic stroke

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Social anxiety and autism spectrum traits among adult FMR1 premutation carriers.

Behavioral symptoms and traits have been proposed as early markers in neurodegenerative diseases. The aim of this study was to evaluate social anxiety and autism in FMR1 premutation carriers using the Social Phobia Inventory (SPIN) and the Autism-Spectrum Quotient (AQ) questionnaires. Fifty-nine premutation carriers were compared with 50 controls. The SPIN test showed statistically significant differences between female but not male carriers. The AQ questionnaire found statistically significant differences between premutation carriers and controls in the total AQ as well as in the social skills and attention switching subdomains. A gender effect was only observed for the social skills subdomain. Spearman's correlation analysis revealed a moderately positive correlation with the total AQ scores as well as the social skills and communication subdomains. Our results show that fragile X-associated tremor/ataxia syndrome (FXTAS) patients have higher AQ scores. Moreover, this is the first study to find statistically significant differences between FXTAS and no-FXTAS premutation carriers in the communication and the imagination subdomains, suggesting that FXTAS patients present a broader autistic phenotype than premutation carriers without FXTAS. Based on our results, a wide range of behavioral/psychiatric traits should be included within the broader phenotypic presentation of individuals with the FMR1 premutation.

White matter alterations in the brains of patients with active, remitted, and cured cushing syndrome: a DTI study.

BACKGROUND AND PURPOSE: Cushing syndrome appears after chronic exposure to elevated glucocorticoid levels. Cortisol excess may alter white matter microstructure. Our purpose was to study WM changes in patients with Cushing syndrome compared with controls by using DTI and the influence of hypercortisolism. MATERIALS AND METHODS: Thirty-five patients with Cushing syndrome and 35 healthy controls, matched for age, education, and sex, were analyzed through DTI (tract-based spatial statistics) for fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity (general linear model, family-wise error, and threshold-free cluster enhancement corrections, P < .05). Furthermore, the influence of hypercortisolism on WM DTI changes was studied by comparing 4 subgroups: 8 patients with Cushing syndrome with active hypercortisolism, 7 with Cushing syndrome with medication-remitted cortisol, 20 surgically cured, and 35 controls. Cardiovascular risk factors were used as covariates. In addition, correlations were analyzed among DTI values, concomitant 24-hour urinary free cortisol levels, and disease duration. RESULTS: There were widespread alterations (reduced fractional anisotropy, and increased mean diffusivity, axial diffusivity, and radial diffusivity values; P < .05) in patients with Cushing syndrome compared with controls, independent of the cardiovascular risk factors present. Both active and cured Cushing syndrome subgroups showed similar changes compared with controls. Patients with medically remitted Cushing syndrome also had reduced fractional anisotropy and increased mean diffusivity and radial diffusivity values, compared with controls. No correlations were found between DTI maps and 24-hour urinary free cortisol levels or with disease duration. CONCLUSIONS: Diffuse WM alterations in patients with Cushing syndrome suggest underlying loss of WM integrity and demyelination. Once present, they seem to be independent of concomitant hypercortisolism, persisting after remission/cure.

Improving the execution performance of FreeSurfer : a new scheduled pipeline scheme for optimizing the use of CPU and GPU resources.

A scheme to significantly speed up the processing of MRI with FreeSurfer (FS) is presented. The scheme is aimed at maximizing the productivity (number of subjects processed per unit time) for the use case of research projects with datasets involving many acquisitions. The scheme combines the already existing GPU-accelerated version of the FS workflow with a task-level parallel scheme supervised by a resource scheduler. This allows for an optimum utilization of the computational power of a given hardware platform while avoiding problems with shortages of platform resources. The scheme can be executed on a wide variety of platforms, as its implementation only involves the script that orchestrates the execution of the workflow components and the FS code itself requires no modifications. The scheme has been implemented and tested on a commodity platform within the reach of most research groups (a personal computer with four cores and an NVIDIA GeForce 480 GTX graphics card). Using the scheduled task-level parallel scheme, a productivity above 0.6 subjects per hour is achieved on the test platform, corresponding to a speedup of over six times compared to the default CPU-only serial FS workflow.

Microstructural white-matter abnormalities associated with treatment resistance, severity and duration of illness in major depression.

BACKGROUND: Although white-matter abnormalities have been reported in middle-aged patients with major depressive disorder (MDD), few data are available on treatment-resistant MDD and the influence of relevant variables related to clinical burden of illness is far from being well established. METHOD: The present study examined white-matter microstructure in a sample of 52 patients with MDD in different stages (treatment-resistant/chronic MDD, n = 18; remitted-recurrent MDD, n = 15; first-episode MDD, n = 19) and 17 healthy controls, using diffusion tensor imaging with a tract-based spatial statistics approach. Groups were comparable in age and gender distribution, and results were corrected for familywise error (FWE) rate. RESULTS: Widespread significant reductions of fractional anisotropy (FA) - including the cingulum, corpus callosum, superior and inferior longitudinal fascicule - were evident in treatment-resistant/chronic MDD compared with first-episode MDD and controls (p < 0.05, FWE-corrected). Decreased FA was observed within the ventromedial prefrontal region in treatment-resistant/chronic MDD even when compared with the remitted-recurrent MDD group (p < 0.05, FWE-corrected). Longer duration of illness (ß = -0.49, p = 0.04) and higher depression severity (at a trend level: ß = -0.26, p = 0.06) predicted lower FA in linear multiple regression analysis at the whole-brain level. The number of previous episodes and severity of symptoms were significant predictors when focused on the ventromedial prefrontal area (ß = -0.28, p = 0.04; and ß = -0.29, p = 0.03, respectively). Medication effects were controlled for in the analyses and results remained unaltered. CONCLUSIONS: Our findings support the notion that disruptions of white-matter microstructure, particularly in fronto-limbic networks, are associated with resistance to treatment and higher current and past burden of depression.

Motor and mental dysfunction in mother-daughter transmitted FXTAS.

OBJECTIVES: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neuropsychiatric degenerative disorder that occurs predominantly in male FMR1 premutation carriers. Recently, a broader FXTAS spectrum that, besides the core features of tremor and gait ataxia, also includes neuropsychiatric symptoms and neuropathy as further clinically relevant symptoms has been described among females. Herein 2 fragile X syndrome families with a mother-daughter FXTAS transmission are described in detail in order to shed more light on the female FXTAS phenotype. METHODS: Molecular characterization included CGG repeat length, X-chromosome inactivation pattern determination, as well as FMR1 mRNA and FMRP levels quantification. Neuroradiologic examination was performed by 3-T MRI. Neuropsychological assessment included global cognitive, attention, and executive prefrontal functions, verbal fluencies, verbal memory, and visuospatial perception. RESULTS: Molecular, neurologic, neuropsychiatric, psychological, cognitive, and neuroradiologic features description of 2 fragile X syndrome families with a mother-daughter FXTAS transmission in which dementia is present in both mothers. CONCLUSIONS: Although it is not yet clear to what extent FXTAS shortens lifespan, our findings show that FXTAS progresses from mild tremor and/or ataxia to disabling motor and cognitive impairment, compromising the patients' quality of life. Furthermore, our results show that FXTAS in women can also develop as a multisystem neurodegenerative disorder with central and peripheral nervous system involvement, and both motor and mental disturbances.

Problem-solving abilities and frontal lobe cortical thickness in healthy aging and mild cognitive impairment.

Mild cognitive impairment (MCI) is considered a transitional state between normal aging and Alzheimer disease. Most MCI subjects present disturbances in multiple neuropsychological domains, including executive function. This study aimed at exploring frontal lobe cortical thinning in MCI and healthy controls, and its relationship with problem-solving abilities. Twenty-three MCI patients and 30 elderly controls underwent MRI and neuropsychological assessment. Cortical thickness was measured by means of FreeSurfer. Problem-solving was assessed by means of the Tower of London (TOL) task. MCI showed a global thinning of the cortex. With regard to specific regions of interest, a thinning in the left frontal lobe and the bilateral posterior cingulate gyri was found. Partial correlations, after controlling for age, education, Mini-Mental Status Examination, and non-frontal mean thickness revealed negative significant correlations between frontal lobe thickness and executive outcomes in the control group. This counterintuitive relationship was not observed in the MCI group, suggesting that the frontal cortical atrophy observed in MCI entails a specific pathology-related relationship with high-level executive outcomes that is qualitatively different from that observed in healthy aging.

Prefrontal cortex volume reduction on MRI in preclinical Huntington's disease relates to visuomotor performance and CAG number.

PURPOSE: To investigate grey matter volumes on magnetic resonance imaging (MRI) in preclinical Huntington's disease (HD), and their relationship to neuropsychology and CAG number. MATERIAL AND METHODS: Twenty preclinical HD carriers and 21 healthy controls matched for age, sex, and educational level were included in this study. Clinical (UHDRS), and detailed neuropsychological assessments, and 3D IR SPGR axial MR acquisition. Calculation of global, segmented (SIENAX), and focal (voxel based morphometry, VBM) grey matter volumes was carried out. An analysis of variance (ANOVA) and a general linear model for VBM analysis were used to compare preclinical HD carriers and controls. Small volume correction was used, and clusters at p<0.05 were considered significant. Correlation analysis (VBM) with neuropsychology, and CAG number was also performed. RESULTS: Preclinical HD carriers showed, compared to controls, smaller global volumes of the brain (1279+/-6 vs. 1331+/-46, p=0.003), total (666+/-48 vs. 698+/-34, p=0.020) and cortical grey matter (551+/-44 vs. 577+/-32, p=0.035). When compared to the controls, preclinical carriers showed focal volume losses, which were more prominent in the left prefrontal cortex, cerebellum, and right posterior temporal cortex. Preclinical HD performed slower in a visuomotor integration task, the 15-Objects test, than controls (t (1,25.02)=3.69; p=0.001: pre-HD: 69.55+/-28.86; controls: 45.79+/-8.38). A correlation was found between volume loss in the prefrontal cortex, visuomotor performance, and CAG number. CONCLUSION: Preclinical HD carriers show grey matter volume reduction involving the prefrontal cortex, which relates to the visuomotor performance and CAG number. This suggests that regionally selective neuronal loss/dysfunction occurs prior to the clinical onset of symptoms.