Is Period3 Genotype Associated With Sleep and Recovery in Patients With Disorders of Consciousness?

Background Sleep evaluation is increasingly being used as prognostic tool in patients with disorders of consciousness, but, surprisingly, the role of Period3 (Per3) gene polymorphism has never been evaluated. Objective The aim of this study was to investigate the contribution of Per3 genotype on sleep quantity and consciousness recovery level in patients with disorders of consciousness (DOC). Methods In this observational study, we evaluated 71 patients with DOC classified as vegetative state/unresponsive wakefulness syndrome or minimally conscious state. Demographic and clinical data were collected and a standardised diagnostic workup, including a polysomnographic record, was applied. After informed consent provided by proxy, genomic DNA was obtained and Per3 polymorphism was analysed by polymerase chain reaction to identify 5/5, 4/5, or 4/4 genotype. Results Per3(5/5) genotype was found in 12.7% of our DOC patients. The median total Coma Recovery Scale-revised score in Per3(5/5) carriers was significantly higher than 4/4 genotype (10, range 5-16 vs 7, range 4-11; post hoc P = .036). Moreover, total sleep time seemed to be higher in 5/5 genotype (5/5, 221 minutes, range 88-515 minutes; 4/4, 151.5 minutes, range 36-477 minutes; and 4/5, 188 minutes, range 44-422 minutes). Conclusion For the first time we have shown a possible association between Per3 polymorphism and consciousness recovery level in DOC patients. Even though the exact molecular mechanism has not been defined, we speculate that its effect is mediated by higher total sleep time and slow wave sleep, which would improve the preservation of main cerebral connections.

Assessment of patients with disorder of consciousness: do different Coma Recovery Scale scoring correlate with different settings?

Differential diagnosis between Vegetative State and Minimally Conscious State is a challenging task that requires specific assessment scales, involvement of expert neuropsychologists or physicians and use of tailored stimuli for eliciting behavioural responses. Although misdiagnosis rate as high as 40% has been reported, no clear guidelines are available in literature on the optimal setting for assessment. The present study aims to analyse score differences in behavioural assessments of persons with disorders of consciousness (DOC) with or without family members and to determine whether the presence of caregivers could improve clinical accuracy in diagnostic evaluation. The research was conducted on 92 adults with DOC among 153 consecutive patients enrolled in the Coma Research Centre of the Neurological Institute C. Besta of Milan between January 2011 and May 2013. The results indicate that in almost half of the sample the scoring, thus the performance, observed with caregivers was better than without them. Furthermore, in 16% of the sample, when assessment was performed with caregivers there was a change in diagnosis, from Vegetative to Minimally Conscious State or from that to Severe Disability. Finally, statistical differences were found in relation to diagnosis between mean scores in the "visual function" Coma Recovery Scale revised's subscale obtained by raters plus caregiver and rates only assessment. This study demonstrates how the presence of caregivers can positively affect behavioural assessments of persons with DOC, thus contributing to the definition of the optimal setting for behavioural evaluation of patients, to decrease misdiagnosis rates.

Visual neglect as a disconnection syndrome? A confirmatory case report.

Visual neglect has classically been associated with right hemisphere injury in parietal, frontal, or temporal cortex, in the basal ganglia or in the thalamus. More recently, visual neglect has been associated with injury extended into fronto-parietal white matter tracts. However, in most published cases white and gray matter injuries were associated. We present the anatomo-clinical study of a patient presenting with severe acute left visual neglect due to ischemic infarct limited to the right cerebral hemisphere white matter. Magnetic resonance diffusion tensor imaging tractography was instrumental to accurately localize the injury to the right arcuate fasciculus that is a component of the large-scale networks controlling visuo-spatial attention. These results add to a growing appreciation that neglect may result from disruption of a distributed attentional network.

Is 'object-centred neglect' a homogeneous entity?

The nature of object-centred (allocentric) neglect and the possibility of dissociating it from egocentric (subject-centred) forms of neglect are controversial. Originally, allocentric neglect was described by Gainotti, D'Erme, Monteleone & Silveri (1986) and Gainotti, Messerli, & Tissot (1972) in patients who reproduced all the elements of a multi-object scene, but left unfinished the left side of one or more of them. More recently, however, Karnath, Mandler, and Clavagnier (2011) have claimed that the severity of allocentric neglect worsens when a complex 'object' shifts from an ipsilesional to a contralesional egocentric position. On the basis of these and of other clinical data, showing that allocentric and egocentric neglect are strongly associated, they have questioned the possibility of dissociating these two forms of neglect, suggesting that egocentric and allocentric neglect constitute different manifestations of the same disturbed system. Since these statements were inconsistent with the clinical findings which had prompted the construct of object-centred neglect, we checked in a group of right brain-damaged patients, who had copied the original multi-object scene, if the degree of neglect for the left side of figures varied as a function of their position on the horizontal axis. Furthermore, we reviewed all papers where copies of other multi-object scenes had been reported. Results of both studies failed to confirm the assumption of a relationship between spatial location of the stimulus and severity of object-centred neglect. This discrepancy between our data and those obtained by Karnath et al. (2011) could be due to the characteristics of stimuli and of procedures used to evaluate 'object-centred' neglect. If the stimulus is complex and the task requires its thorough exploration, the spatial location of the stimulus will influence the severity of 'object-centred neglect'. If, on the contrary, the stimulus is simple and can be identified with few eye fixations, the spatial location of the stimulus should not influence the severity of 'object-centred neglect'. In any case, our data confirm the possibility of dissociating allocentric from egocentric neglect.

Aphasia induced by gliomas growing in the ventrolateral frontal region: assessment with diffusion MR tractography, functional MR imaging and neuropsychology.

INTRODUCTION: Lesions in the ventrolateral region of the dominant frontal lobe have been historically associated with aphasia. Recent imaging results suggest that frontal language regions extend beyond classically defined Broca's area to include the ventral precentral gyrus (VPCG) and the arcuate fasciculus (AF). Frontal gliomas offer a unique opportunity to identify structures that are essential for speech production. The aim of this prospective study was to investigate the correlation between language deficits and lesion location in patients with gliomas. METHODS: Nineteen patients with glioma and 10 healthy subjects were evaluated with diffusion tensor imaging magnetic resonance (MR) tractography, functional MR (verb generation task) and the Aachener Aphasie Test. Patients were divided into two groups according to lesion location with respect to the ventral precentral sulcus: (i) anterior (n=8) with glioma growing in the inferior frontal gyrus (IFG) and underlying white matter; (ii) posterior (n=11) with glioma growing in the VPCG and underlying white matter. Virtual dissection of the AF, frontal intralobar tract, uncinate fasciculus (UF) and inferior frontal occipital fasciculus (IFOF) was performed with a deterministic approach. RESULTS: Seven posterior patients showed aphasia classified as conduction (4), Broca (1), transcortical motor (1) and an isolated deficit of semantic fluency; one anterior patient had transcortical mixed aphasia. All posterior patients had invasion of the VPCG, however only patients with aphasia had also lesion extension to the AF as demonstrated by tractography dissections. All patients with language deficits had high grade glioma. Groups did not differ regarding tumour volume. A functional pars opercularis was identified with functional MR imaging (fMRI) in 17 patients. CONCLUSIONS: Gliomas growing in the left VPCG are much more likely to cause speech deficits than gliomas infiltrating the IFG, including Broca's area. Lesion extension to the AF connecting frontal to parietal and temporal regions is an important mechanism for the appearance of aphasia.

Different views about the nature of gender-related asymmetries in tasks based on biological or artefact categories.

Sex-related asymmetries in the ability to process different semantic categories have been reported both in normal subjects and in brain-damaged patients, but the nature of these asymmetries is still controversial. Some authors suggest that these differences might be due to social-role related familiarity factors, whereas others attribute them to inborn neural differences rooted in evolution. Drawing in part on this second line of thought, some authors have suggested that gender-related asymmetries might be due to differences in stimulus processing between men and women, namely, to the tendency of females to focus mainly on perceptual features and of males to focus equally on both perceptual and functional features. To test this hypothesis, we asked 53 male and 65 female undergraduate students to evaluate the relevance of a number of perceptual and functional features in the representation of various kinds of biological and artefact categories. Contrary to the hypothesis, evaluation of the weight of different sources of knowledge in representing living and artefact categories was similar in males and females.

Mental representation of normal subjects about the sources of knowledge in different semantic categories and unique entities.

According to the "sensory-motor model of semantic knowledge," different categories of knowledge differ for the weight that different "sources of knowledge" have in their representation. Our study aimed to evaluate this model, checking if subjective evaluations given by normal subjects confirm the different weight that various sources of knowledge have in the representation of different biological and artifact categories and of unique entities, such as famous people or monuments. Results showed that the visual properties are considered as the main source of knowledge for all the living and nonliving categories (as well as for unique entities), but that the clustering of these "sources of knowledge" is different for biological and artifacts categories. Visual data are, indeed, mainly associated with other perceptual (auditory, olfactory, gustatory, and tactual) attributes in the mental representation of living beings and unique entities, whereas they are associated with action-related properties and tactile information in the case of artifacts.

Circulating and thymic CD4 CD25 T regulatory cells in myasthenia gravis: effect of immunosuppressive treatment.

Accumulating evidence indicates an immunosuppressive role of the thymus-derived CD4+ T-cell population constitutively expressing high level of CD25, T regulatory (Treg) cells, in autoimmune diseases. Here we show that the number of Treg cells in the blood is significantly lower in untreated myasthenia gravis patients than in age-matched healthy subjects, whereas it is normal or elevated in patients on immunosuppressive therapy (prednisone frequently associated with azathioprine). Therapeutic thymectomy (Tx) for either the thymoma or non-neoplastic thymic alterations that are often associated with myasthenia gravis provided unique material for studying intrathymic Treg cells and correlating them with their peripheral counterparts. We observed that Tx prevents the increase of Treg cells in the circulation that follows immunosuppressive therapy (particularly evident if the thymus is not neoplastic), indicating that the thymus contributes to Treg-cell normalization. However, thymic Treg cells are not modulated by immunosuppressive therapy and even in thymectomized patients Treg-cell numbers in the blood eventually recover. The present findings suggest that a deficiency in Treg cells favours the development of myasthenia gravis and that their normalization is an important clinical benefit of immunosuppressive therapy. Treg normalization appears to be largely thymus independent and possibly reflects the reported capacity of corticosteroids to promote Treg-cell development.