Theory of mind after mild TBI in preschool children : a longitudinal perspective

Les enfants d’âge préscolaire (≤ 5 ans) sont plus à risque de subir un traumatisme crânio-cérébral (TCC) que les enfants plus agés, et 90% de ces TCC sont de sévérité légère (TCCL). De nombreuses études publiées dans les deux dernières décennies démontrent que le TCCL pédiatrique peut engendrer des difficultés cognitives, comportementales et psychiatriques en phase aigüe qui, chez certains enfants, peuvent perdurer à long terme. Il existe une littérature florissante concernant l'impact du TCCL sur le fonctionnement social et sur la cognition sociale (les processus cognitifs qui sous-tendent la socialisation) chez les enfants d'âge scolaire et les adolescents. Or, seulement deux études ont examiné l'impact d'un TCCL à l'âge préscolaire sur le développement social et aucune étude ne s'est penchée sur les répercussions socio-cognitives d'un TCCL précoce (à l’âge préscolaire). L'objectif de la présente thèse était donc d'étudier les conséquences du TCCL en bas âge sur la cognition sociale. Pour ce faire, nous avons examiné un aspect de la cognition sociale qui est en plein essor à cet âge, soit la théorie de l'esprit (TE), qui réfère à la capacité de se mettre à la place d'autrui et de comprendre sa perspective. Le premier article avait pour but d'étudier deux sous-composantes de la TE, soit la compréhension des fausses croyances et le raisonnement des désirs et des émotions d'autrui, six mois post-TCCL. Les résultats indiquent que les enfants d'âge préscolaire (18 à 60 mois) qui subissent un TCCL ont une TE significativement moins bonne 6 mois post-TCCL comparativement à un groupe contrôle d'enfants n'ayant subi aucune blessure. Le deuxième article visait à éclaircir l'origine de la diminution de la TE suite à un TCCL précoce. Cet objectif découle du débat qui existe actuellement dans la littérature. En effet, plusieurs scientifiques sont d'avis que l'on peut conclure à un effet découlant de la blessure au cerveau seulement lorsque les enfants ayant subi un TCCL sont comparés à des enfants ayant subi une blessure n'impliquant pas la tête (p.ex., une blessure orthopédique). Cet argument est fondé sur des études qui démontrent qu'en général, les enfants qui sont plus susceptibles de subir une blessure, peu importe la nature de celle-ci, ont des caractéristiques cognitives pré-existantes (p.ex. impulsivité, difficultés attentionnelles). Il s'avère donc possible que les difficultés que nous croyons attribuables à la blessure cérébrale étaient présentes avant même que l'enfant ne subisse un TCCL. Dans cette deuxième étude, nous avons donc comparé les performances aux tâches de TE d'enfants ayant subi un TCCL à ceux d'enfants appartenant à deux groupes contrôles, soit des enfants n'ayant subi aucune blessure et à des pairs ayant subi une blessure orthopédique. De façon générale, les enfants ayant subi un TCCL ont obtenu des performances significativement plus faibles à la tâche évaluant le raisonnement des désirs et des émotions d'autrui, 6 mois post-blessure, comparativement aux deux groupes contrôles. Cette étude visait également à examiner l'évolution de la TE suite à un TCCL, soit de 6 mois à 18 mois post-blessure. Les résultats démontrent que les moindres performances sont maintenues 18 mois post-TCCL. Enfin, le troisième but de cette étude était d’investiguer s’il existe un lien en la performance aux tâches de TE et les habiletés sociales, telles qu’évaluées à l’aide d’un questionnaire rempli par le parent. De façon intéressante, la TE est associée aux habiletés sociales seulement chez les enfants ayant subi un TCCL. Dans l'ensemble, ces deux études mettent en évidence des répercussions spécifiques du TCCL précoce sur la TE qui persistent à long terme, et une TE amoindrie seraient associée à de moins bonnes habiletés sociales. Cette thèse démontre qu'un TCCL en bas âge peut faire obstacle au développement sociocognitif, par le biais de répercussions sur la TE. Ces résultats appuient la théorie selon laquelle le jeune cerveau immature présente une vulnérabilité accrue aux blessures cérébrales. Enfin, ces études mettent en lumière la nécessité d'étudier ce groupe d'âge, plutôt que d'extrapoler à partir de résultats obtenus avec des enfants plus âgés, puisque les enjeux développementaux s'avèrent différents, et que ceux-ci ont potentiellement une influence majeure sur les répercussions d'une blessure cérébrale sur le fonctionnement sociocognitif.

Graph analysis of verbal fluency test discriminate between patients with Alzheimer’s disease, Mild Cognitive Impairment and normal elderly controls

Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment – subtypes amnestic(aMCI) and amnestic multiple domain (a+mdMCI) - and patients with Alzheimer’s disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGAs). The individuals were compared when divided in three (NC – MCI – AD) and four (NC – aMCI – a+mdMCI – AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of semantic memory through the verbal fluency task, with potential to amplify the predictive power of this test. Graph analysis is likely to become clinically relevant in neurology and psychiatry, and may be particularly useful for the differential diagnosis of the elderly.

Confirmation of Elsey virus infection in a Queensland horse with mild neurologic signs

In 2011, a 2-year-old horse in northern Queensland, Australia, was reported to have developed mild neurologic signs, and a blood sample was submitted for laboratory investigation. Virus isolation was performed using the blood sample, and an orbivirus was isolated. This was confirmed to be a strain of Elsey virus (ELSV) after transmission electron microscopy and nucleotide sequencing. The nucleotide sequence was compared with those in GenBank, and had 100% identity with ELSV previously reported from the Northern Territory, Australia. ELSV is taxonomically closely related to Peruvian horse sickness virus.

Transcriptome, carbohydrate, and phytohormone analysis of Petunia hybrida reveals a complex disturbance of plant functional integrity under mild chilling stress

Cultivation of chilling-tolerant ornamental crops at lower temperature could reduce the energy demands of heated greenhouses. To provide a better understanding of how sub-optimal temperatures (12 degrees C vs. 16 degrees C) affect growth of the sensitive Petunia hybrida cultivar 'SweetSunshine Williams', the transcriptome, carbohydrate metabolism, and phytohormone homeostasis were monitored in aerial plant parts over 4 weeks by use of a microarray, enzymatic assays and GC-MS/MS. The data revealed three consecutive phases of chilling response. The first days were marked by a strong accumulation of sugars, particularly in source leaves, preferential up-regulation of genes in the same tissue and down-regulation of several genes in the shoot apex, especially those involved in the abiotic stress response. The midterm phase featured a partial normalization of carbohydrate levels and gene expression. After 3 weeks of chilling exposure, a new stabilized balance was established. Reduced hexose levels in the shoot apex, reduced ratios of sugar levels between the apex and source leaves and a higher apical sucrose/hexose ratio, associated with decreased activity and expression of cell wall invertase, indicate that prolonged chilling induced sugar accumulation in source leaves at the expense of reduced sugar transport to and reduced sucrose utilization in the shoot. This was associated with reduced levels of indole-3-acetic acid and abscisic acid in the apex and high numbers of differentially, particularly up-regulated genes, especially in the source leaves, including those regulating histones, ethylene action, transcription factors, and a jasmonate-ZIM-domain protein. Transcripts of one Jumonji C domain containing protein and one expansin accumulated in source leaves throughout the chilling period. The results reveal a dynamic and complex disturbance of plant function in response to mild chilling, opening new perspectives for the comparative analysis of differently tolerant cultivars.

Graph analysis of verbal fluency test discriminate between patients with Alzheimer’s disease, Mild Cognitive Impairment and normal elderly controls

Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment – subtypes amnestic(aMCI) and amnestic multiple domain (a+mdMCI) - and patients with Alzheimer’s disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGAs). The individuals were compared when divided in three (NC – MCI – AD) and four (NC – aMCI – a+mdMCI – AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of semantic memory through the verbal fluency task, with potential to amplify the predictive power of this test. Graph analysis is likely to become clinically relevant in neurology and psychiatry, and may be particularly useful for the differential diagnosis of the elderly.

Randomised controlled trial of short bursts of a potent topical corticosteroid versus prolonged use of a mild preparation for children with mild or moderate atopic eczema

Objective To determine whether a three day burst of a potent corticosteroid is more effective than a mild preparation used for seven days in children with mild or moderate atopic eczema. Design Randomised, double blind, parallel group study of 18 weeks' duration. Setting 13 general practices and a teaching hospital in the Nottingham area. Participants 174 children with mild or moderate atopic eczema recruited from general practices and 33 from a hospital outpatient clinic. Interventions 0.1% betamethasone valerate applied for three days followed by the base ointment for four days versus 1% hydrocortisone applied for seven days. Main outcome measures Primary outcomes were total number of scratch­free days and number of relapses. Secondary outcomes were median duration of relapses, number of undisturbed nights, disease severity (six area, six sign atopic dermatitis severity scale), scores on two quality of life measures (children's life quality index and dermatitis family impact questionnaire), and number of patients in whom treatment failed in each arm. Results No differences were found between the two groups. This was consistent for all outcomes. The median number of scratch­free days was 118.0 for the mild group and 117.5 for the potent group (difference 0.5, 95% confidence interval - 2.0 to 4.0, P = 0.53). The median number of relapses for both groups was 1.0. Both groups showed clinically important improvements in disease severity and quality of life compared with baseline. Conclusion A short burst of a potent topical corticosteroid is just as effective as prolonged use of a milder preparation for controlling mild or moderate atopic eczema in children.

Time perception in mild cognitive impairment: Interval length and subjective passage of time

Objectives: Patients with mild cognitive impairment (MCI) may have difficulties in time perception, which in turn might contribute to some of their symptoms, especially memory deficits. The aim of this study was to evaluate perception of interval length and subjective passage of time in MCI patients as compared to healthy controls. Methods: Fifty-five MCI patients and 57 healthy controls underwent an experimental protocol for time perception on interval length, a questionnaire for the subjective passage of time and a neuropsychological evaluation. Results: MCI patients presented no changes in the perception of interval length. However, for MCI patients, time seemed to pass more slowly than it did for controls. This experience was significantly correlated with memory deficits but not with performance in executive tests, nor with complaints of depression or anxiety. Conclusions: Memory deficits do not affect the perception of interval length, but are associated with alterations in the subjective passage of time.

A novel mutation of AFG3L2 might cause dominant optic atrophy in patients with mild intellectual disability

International audience

Theory of mind after mild TBI in preschool children : a longitudinal perspective

Les enfants d’âge préscolaire (≤ 5 ans) sont plus à risque de subir un traumatisme crânio-cérébral (TCC) que les enfants plus agés, et 90% de ces TCC sont de sévérité légère (TCCL). De nombreuses études publiées dans les deux dernières décennies démontrent que le TCCL pédiatrique peut engendrer des difficultés cognitives, comportementales et psychiatriques en phase aigüe qui, chez certains enfants, peuvent perdurer à long terme. Il existe une littérature florissante concernant l'impact du TCCL sur le fonctionnement social et sur la cognition sociale (les processus cognitifs qui sous-tendent la socialisation) chez les enfants d'âge scolaire et les adolescents. Or, seulement deux études ont examiné l'impact d'un TCCL à l'âge préscolaire sur le développement social et aucune étude ne s'est penchée sur les répercussions socio-cognitives d'un TCCL précoce (à l’âge préscolaire). L'objectif de la présente thèse était donc d'étudier les conséquences du TCCL en bas âge sur la cognition sociale. Pour ce faire, nous avons examiné un aspect de la cognition sociale qui est en plein essor à cet âge, soit la théorie de l'esprit (TE), qui réfère à la capacité de se mettre à la place d'autrui et de comprendre sa perspective. Le premier article avait pour but d'étudier deux sous-composantes de la TE, soit la compréhension des fausses croyances et le raisonnement des désirs et des émotions d'autrui, six mois post-TCCL. Les résultats indiquent que les enfants d'âge préscolaire (18 à 60 mois) qui subissent un TCCL ont une TE significativement moins bonne 6 mois post-TCCL comparativement à un groupe contrôle d'enfants n'ayant subi aucune blessure. Le deuxième article visait à éclaircir l'origine de la diminution de la TE suite à un TCCL précoce. Cet objectif découle du débat qui existe actuellement dans la littérature. En effet, plusieurs scientifiques sont d'avis que l'on peut conclure à un effet découlant de la blessure au cerveau seulement lorsque les enfants ayant subi un TCCL sont comparés à des enfants ayant subi une blessure n'impliquant pas la tête (p.ex., une blessure orthopédique). Cet argument est fondé sur des études qui démontrent qu'en général, les enfants qui sont plus susceptibles de subir une blessure, peu importe la nature de celle-ci, ont des caractéristiques cognitives pré-existantes (p.ex. impulsivité, difficultés attentionnelles). Il s'avère donc possible que les difficultés que nous croyons attribuables à la blessure cérébrale étaient présentes avant même que l'enfant ne subisse un TCCL. Dans cette deuxième étude, nous avons donc comparé les performances aux tâches de TE d'enfants ayant subi un TCCL à ceux d'enfants appartenant à deux groupes contrôles, soit des enfants n'ayant subi aucune blessure et à des pairs ayant subi une blessure orthopédique. De façon générale, les enfants ayant subi un TCCL ont obtenu des performances significativement plus faibles à la tâche évaluant le raisonnement des désirs et des émotions d'autrui, 6 mois post-blessure, comparativement aux deux groupes contrôles. Cette étude visait également à examiner l'évolution de la TE suite à un TCCL, soit de 6 mois à 18 mois post-blessure. Les résultats démontrent que les moindres performances sont maintenues 18 mois post-TCCL. Enfin, le troisième but de cette étude était d’investiguer s’il existe un lien en la performance aux tâches de TE et les habiletés sociales, telles qu’évaluées à l’aide d’un questionnaire rempli par le parent. De façon intéressante, la TE est associée aux habiletés sociales seulement chez les enfants ayant subi un TCCL. Dans l'ensemble, ces deux études mettent en évidence des répercussions spécifiques du TCCL précoce sur la TE qui persistent à long terme, et une TE amoindrie seraient associée à de moins bonnes habiletés sociales. Cette thèse démontre qu'un TCCL en bas âge peut faire obstacle au développement sociocognitif, par le biais de répercussions sur la TE. Ces résultats appuient la théorie selon laquelle le jeune cerveau immature présente une vulnérabilité accrue aux blessures cérébrales. Enfin, ces études mettent en lumière la nécessité d'étudier ce groupe d'âge, plutôt que d'extrapoler à partir de résultats obtenus avec des enfants plus âgés, puisque les enjeux développementaux s'avèrent différents, et que ceux-ci ont potentiellement une influence majeure sur les répercussions d'une blessure cérébrale sur le fonctionnement sociocognitif.

Delay discounting in mild cognitive impairment

Introduction : Patients with mild cognitive impairme nt (MCI) may make suboptimal decisions particularly in complex situations, and thi s could be due to temporal discounting, the tendency to prefer immediate rewards over delayed but larger rewards. The present study proposes to evaluate intertemporal prefere nces in MCI patients as compared to healthy controls. Method : Fifty-five patients with MCI and 57 h ealthy controls underwent neuropsy- chological evaluation and a delay discounting questionnaire, which evaluates three para- meters: hyperbolic discounting ( k ), the percentage of choices for delayed and later rewards (%LL), and response consistency (Acc). Results : No significant differences were found in the delay discounting questionnaire between MC I patients and controls for the three reward sizes considered, small, medium, and large, using both k and %LL parameters. There were also no differences in the response consistency, Acc, between the two groups. Conclusions : Patients with MCI perform similarly to healthy controls in a delay discounting task. Memory deficits do not notably affect intertemporal preferences.

Effect of telmisartan on functional outcome, recurrence, and blood pressure in patients with acute mild ischemic stroke: a PRoFESS subgroup analysis

Background and Purpose—High blood pressure (BP) is common in acute ischemic stroke and associated independently with a poor functional outcome. However, the management of BP acutely remains unclear because no large trials have been completed. Methods—The factorial PRoFESS secondary stroke prevention trial assessed BP-lowering and antiplatelet strategies in 20 332 patients; 1360 were enrolled within 72 hours of ischemic stroke, with telmisartan (angiotensin receptor antagonist, 80 mg/d, n647) vs placebo (n713). For this nonprespecified subgroup analysis, the primary outcome was functional outcome at 30 days; secondary outcomes included death, recurrence, and hemodynamic measures at up to 90 days. Analyses were adjusted for baseline prognostic variables and antiplatelet assignment. Results—Patients were representative of the whole trial (age 67 years, male 65%, baseline BP 147/84 mm Hg, small artery disease 60%, NIHSS 3) and baseline variables were similar between treatment groups. The mean time from stroke to recruitment was 58 hours. Combined death or dependency (modified Rankin scale: OR, 1.03; 95% CI, 0.84–1.26; P0.81; death: OR, 1.05; 95% CI, 0.27–4.04; and stroke recurrence: OR, 1.40; 95% CI, 0.68–2.89; P0.36) did not differ between the treatment groups. In comparison with placebo, telmisartan lowered BP (141/82 vs 135/78 mmHg, difference 6 to 7 mmHg and 2 to 4 mmHg; P0.001), pulse pressure (3 to 4 mmHg; P0.002), and rate-pressure product (466 mmHg.bpm; P0.0004). Conclusion—Treatment with telmisartan in 1360 patients with acute mild ischemic stroke and mildly elevated BP appeared to be safe with no excess in adverse events, was not associated with a significant effect on functional dependency, death, or recurrence, and modestly lowered BP.

Macular Thickness as a Potential Biomarker of Mild Alzheimer's Disease

Although several postmortem findings in the retina of patients with Alzheimer's disease (AD) are available, new biomarkers for early diagnosis and follow-up of AD are still lacking. It has been postulated that the defects in the retinal nerve fiber layer (RNFL) may be the earliest sign of AD, even before damage to the hippocampal region that affects memory. This fact may reflect retinal neuronal-ganglion cell death and axonal loss in the optic nerve in addition to aging.

Mild cognitive impairment

Abstract Mild Cognitive Impairment (MCI) is a disease between normal cognitive ageing and dementia. In recent years the term MCI has been recognized as a pre-dementia state, raising an important subject for investigation in the prevention of dementia. There are various terms related to pre-dementia MCI, such as isolated memory complaint and pre-Alzheimer’s disease; most of them do not comprise all the areas related to MCI. A central cholinergic deficit is present in amnestic MCI with neuronal loss in the Meynert basal nucleus. It is estimated that the rate of progression to dementia is about 10% every year. The prevalence of MCI is 10%-11% and the risk of progression to dementia is about 5%-16%. The continual development of pharmacologic approaches to modify and delay the natural history of progression of the disease motivates a great interest in an earlier diagnosis.