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Introduction Following a neurological event, returning to driving is an important activity contributing to improved participation within the community. The purpose of this study was to examine the effectiveness of driving simulator retraining on driving in clients with neurological impairment and to examine factors associated with treatment effectiveness. Method Individuals with non-degenerative brain injury were randomized to either a simulator training or control group. The simulator group received individualized training (16 sessions) using a driving simulator. The control group did not receive intervention. A blind evaluator assessed participants on the DriveAble On-Road Driving Evaluation. Results There was no significant difference between groups in the proportion of individuals who passed the driving evaluation (Chi2 = 0.65; p = 0.42; CI = −0.41 to +0.17). However, participants with moderate impairment who received simulator training were more likely to pass the driving test compared with those in the control group (86% versus 17%; Chi2 = 6.2; p = 0.03; CI = −1.00 to −0.30). There were no differences in pass rate according to diagnosis, gender, or for those with severe impairments. Conclusion Results provide clinicians with preliminary information on the potential clinical usefulness of driving simulator training. While the findings do not support simulator retraining for the group as a whole, they suggest that clients with moderate impairment have the potential to benefit.

International audience; On the basis of phylogenetic analyses, we uncovered a variant of the CDX2 homeobox gene, a major regulator of the development and homeostasis of the gut epithelium, also involved in cancer. This variant, miniCDX2, is generated by alternative splicing coupled to alternative translation initiation, and contains the DNA-binding homeodomain but is devoid of transactivation domain. It is predominantly expressed in crypt cells, whereas the CDX2 protein is present in crypt cells but also in differentiated villous cells. Functional studies revealed a dominant-negative effect exerted by miniCDX2 on the transcriptional activity of CDX2, and conversely similar effects regarding several transcription-independent functions of CDX2. In addition, a regulatory role played by the CDX2 and miniCDX2 homeoproteins on their pre-mRNA splicing is displayed, through interactions with splicing factors. Overexpression of miniCDX2 in the duodenal Brunner glands leads to the expansion of the territory of these glands and ultimately to brunneroma. As a whole, this study characterized a new and original variant of the CDX2 homeobox gene. The production of this variant represents not only a novel level of regulation of this gene, but also a novel way to fine-tune its biological activity through the versatile functions exerted by the truncated variant compared to the full-length homeoprotein. This study highlights the relevance of generating protein diversity through alternative splicing in the gut and its diseases. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

International audience; The vast majority of cancer deaths are caused by the formation of metastases rather than the primary tumor itself. Despite this clinical importance, the molecular and cellular events that support the dissemination of cancer cells are not yet fully unraveled. We have previously shown that CDX2, a homeotic transcription factor essential for gut development, acts as a colon-specific tumor suppressor and opposes metastasis. Here, using a combination of biochemical, biophysical, and immunofluorescence techniques, we further investigated the mechanisms promoted by CDX2 that might antagonize tumor cell dissemination. We found that CDX2 expression regulates the transcription of RHO GEFs, thereby activating RHO signaling cascades that lead to reorganization of the actin cytoskeleton and enhanced adherent junctions. Accordingly, we observed by atomic force microscopy (AFM) that colon cancer cells expressing CDX2 are less deformable, a feature that has been shown to correlate with poor metastatic potential. Thus, this study illustrates how the loss of expression of a transcription factor during colon cancer progression modifies the biomechanical characteristics of tumor cells and hence facilitates invasion and metastasis.

Cdx2, a gene of the paraHox cluster, encodes a homeodomain transcription factor that plays numerous roles in embryonic development and in homeostasis of the adult intestine. Whereas Cdx2 exerts a tumor suppressor function in the gut, its abnormal ectopic expression in acute leukemia is associated to a pro-oncogenic function. To try to understand this duality, we have hypothesized that Cdx2 may interact with different protein partners in the two tissues and set up experiments to identify them by tandem affinity purification. We show here that Cdx2 interacts with the Ku heterodimer specifically in intestinal cells, but not in leukemia cells, via its homeodomain. Ku proteins do not affect Cdx2 transcriptional activity. However, Cdx2 inhibits in vivo and in vitro the DNA repair activity mediated by Ku proteins in intestinal cells. Whereas Cdx2 does not affect the recruitment of Ku proteins and DNA-PKcs into the DNA repair complex, it inhibits DNA-PKcs activity. Thus, we report here a new function of Cdx2, acting as an inhibitor of the DNA repair machinery, that may contribute to its tumor suppressor function specifically in the gut.

The mechanisms that determine organ identity along the digestive tract in humans are poorly understood. Here we describe the rare case of a young patient who presented with congenital gastric-type heteroplasia in the midjejunum. The lesions, located along the antimesenteric midline of the gut, were made of histologically and functionally normal gastric epithelium without inflammation or in situ/invasive carcinoma. They resembled the anatomy of the lesions developing in the mouse gut as a result of haploinsufficiency of the Cdx2 homeobox gene. The lesions were devoid of CDX2 but without mutation in the coding sequence or in a cis-regulatory element required for intestine-specific expression. Combining these data with the CDX2 expression pattern established from human embryos and cases of Meckel diverticula, we propose a scenario for this patient's presentation, in which CDX2 was missing at the site of ventral closure during gut morphogenesis, with subsequent default differentiation into gastric instead of intestinal tissue. Altogether, these observations argue in favor of a pivotal role played by CDX2 in determining intestinal identity during human embryonic development, as previously shown experimentally in mice.

Homeobox genes, involved in embryonic development and tissues homeostasis in adults, are often deregulated in cancer, but their relevance in pathology is far from being fully elucidated. In colon cancers, we report that the homeoproteins HoxB7 and Cdx2 exhibit different heterogeneous patterns, Cdx2 being localized in moderately altered neoplasic glands in contrast to HoxB7 which predominates in poorly-differentiated areas; they are coexpressed in few cancer cells. In human colon cancer cells, both homeoproteins interact with the DNA repair factor KU70/80, but functional studies reveal opposite effects: HoxB7 stimulates DNA repair and cell survival upon etoposide treatment, whereas Cdx2 inhibits both processes. The stimulatory effect of HoxB7 on DNA repair requires the transactivation domain linked to the homeodomain involved in the interaction with KU70/80, whereas the transactivation domain of Cdx2 is dispensable for its inhibitory function, which instead needs the homeodomain to interact with KU70/80 and the C-terminal domain. Thus, HoxB7 and Cdx2 respectively use transcription-dependent and -independent mechanisms to stimulate and inhibit DNA repair. In addition, in cells co-expressing both homeoproteins, Cdx2 lessens DNA repair activity through a novel mechanism of inhibition of the transcriptional function of HoxB7, whereby Cdx2 forms a molecular complex with HoxB7 and prevents it to recognize its target in the chromatin. These results point out the complex interplay between the DSB DNA repair activity and the homeoproteins HoxB7 and Cdx2 in colon cancer cells, making the balance between these factors a determinant and a potential indicator of the efficacy of genotoxic drugs.

Resume Les troubles cognitifs et du comportement representent la principale cause de difficulte dans la vie quotidienne des traumatises crâniens. Le developpement de l'Echelle neurocomportementale revisee (NRS-R) a represente un progres important pour evaluer ces troubles avec objectivite. La reproductibilite et la validite de construction de cette echelle ont ete etablies, mais sa validite concourante n'a pas ete etudiee sur la version francaise. Objectifs. – Etudier la validite concourante de la NRS-R par rapport a des tests psychometriques traditionnels. Methodes. – Patients : 104 traumatises crâniens a 52 mois du traumatisme, d'âge moyen 28,5 ans, dont 82 hommes et 22 femmes. Chez 70 % d'entre eux le traumatisme etait severe (Echelle de Glasgow GCS inferieure ou egale a huit). Des correlations bilaterales ont ete recherchees entre la NRS-R et les tests suivants : Tour de Londres (TdL), Trail Making Test (TMT), Wisconsin sorting card test (WCST), batterie d'attention TEA, empans de chiffres, echelles de depression CESD et d'anxiete STAI. Resultats. – le facteur Troubles des comportements motives presente des correlations significatives avec la GCS ( p p p p p p p p p p p P p p p p Discussion-Conclusion. – Ainsi que l'etude de Mac Cauley et al. l'avait etabli pour la version anglophone, la NRS-R presente des correlations significatives avec des tests explorant certaines de ses variables, suggerant une bonne validite concourante.

Vanier M, Mazaux J-M, Lambert J, Dassa C, Levin HS. Assessment of neuropsychologic impairments after head injury: interrater reliability and factorial and criterion validity of the Neurobehavioral Rating Scale–Revised (NRS-R). Arch Phys Med Rehabil 2000;81:796-806. Objective: To study interrater reliability and factorial and criterion validity of the Neurobehavioral Rating Scale–Revised (NRS-R). Design: Validity study on persons with traumatic brain injury (TBI) and test-retest reliability study on a randomly selected subset of patients. Factor analyses, kappa statistics, intraclass correlation coefficients, and Cronbach's alphas were used. Setting: Inpatients from 15 French hospitals, mainly rehabilitation units. Other recruitment sites included a neurology hospital unit and a psychiatry hospital specifically devoted to TBI rehabilitation. Patients: Two hundred eighty-six TBI patients ages 16 to 70 years (convenience sample). Results: For the reliability study, the average of percentages of agreement among the items was 74.3% and the average of kappa statistics was.40. Factor analyses disclosed a maximum likelihood extraction of 5 correlated factors (F), explaining 42.2% of total variance: (F1) deficits in intentional behavior and in memory, (F2) lowering of emotional state, (F3) emotional and behavioral hyperactivation, (F4) lowering of arousal state and of attention, and (F5) language and speech problems. Results support the criterion validity of the factors. Reliability of the factor scores and internal consistencies of factors were very good. Conclusions: Results describe some important properties of the NRS-R and, through an understanding of its underlying structure and relationships with the patients' clinical characteristics, contribute to the conceptual framework of neuropsychologic impairments after TBI. © 2000 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Resume En vue d'evaluer l'importance des sequelles neuropsychologiques a long terme des traumatises crâniens, un echantillon de 79 patients a fait l'objet d'une evaluation a 5 ans. Ces sujets etaient issus d'une enquete epidemiologique portant sur 2 116 traumatises cranioencephaliques. L'evaluation des patients a 5 ans, a ete realisee en presence d'un proche, par l'echelle neurocomportementale revisee (NRS-R) et par le document europeen d'evaluation des traumatises crâniens EBIS. Les resultats montrent que chez les traumatises crâniens graves, la fatigabilite mentale, l'humeur depressive, les troubles de la memoire et les troubles des fonctions executives sont les plus frequemment rapportes. Les traumatises crâniens moderes ont un profil a la NRS-R quasi identique a celui des traumatises crâniens legers. Ils souffrent eux aussi de troubles de la memoire, mais dans l'ensemble leur profil neuropsychologique est domine par les troubles affectifs et emotionnels tels que l'humeur depressive, l'anxiete et la labilite de l'humeur. Ces resultats et leur implication dans la prise en charge a long terme de ces patients sont discutes a la lumiere des donnees recentes de la litterature.

This article presents a new instrument, the ADL Pcofile, which is designed specifically for the head injured adult. The instrument is based on the model of occupational performance and on Luria's model of cerebral and motor functioning. It divides the concept of activities of daily living (ADL) into 3 dimensions: personal environment, home environment and community environment. It further delineates a number of activities, tasks and operations under each of these dimensions. The article presents a rationale for the instrument's development, a description of the development process and the preliminary validation work, and details of the instrument itself.

After severe traumatic brain injury, patients almost invariably demonstrate a slowing of reaction time, reflecting a slowing of central information processing. Methodological problems associated with the traditional method for the analysis of longitudinal data (MANOVA) severely complicate studies on cognitive recovery. It is argued that multilevel models are often better suited for the analysis of improvement over time in clinical settings. Multilevel models take into account individual differences in both overall performance level and recovery. These models enable individual predictions for the recovery of speed of information processing. Recovery is modelled in a group of closed-head-injury patients (N = 24). Recovery was predicted by age and severity of injury, as indicated by coma duration. Over a period up to 44 months post trauma, reaction times were found to decrease faster for patients with longer coma duration.

OBJECTIVES. We sought to determine whether the partial administration of the Cognitive Behavioral Driver’s Inventory (CBDI) has a significant effect on its concurrent validity. METHOD. Data were extracted from charts of clients with cerebrovascular accident or traumatic brain injury from three centers. The CBDI was administered either completely or partially (right and left perimetry or Wechsler Adult Intelligence Scale–Revised (WAIS–R; Wechsler, 1982; Picture Completion and Digit Symbol tests were not completed). Concurrent validity indicators were calculated for the CBDI and three different scenarios of partial administration of the CBDI. RESULTS. Only 52% of the road test failures were predicted correctly by the completely administered CBDI. Nonadministration of the WAIS–R rarely modified the CBDI results. Omission of perimetry scores tended to increase the sensitivity and decrease the specificity (not significantly). CONCLUSION. The CBDI should be used as a complement, not a substitution, for a road test. Partially administrating the CBDI, specifically excluding perimetry measures, can affect its concurrent validity.

The recovery of voluntary motor control of the hand following a severe traumatic brain injury was assessed in 31 patients (22 males and 9 females) at three time intervals: within 1 month of the injury, and at 3 and 6 months post-injury. Each patient's performance (could, could not complete) on four motor tasks was assessed: grasp with a stimulus (GWS), grasp without a stimulus (GWOS), release without a stimulus (RWOS) and release with a stimulus (RWS) for both the left and right hands. Significant differences (McNemar chi-square, P

This article presents a new instrument, the ADL Pcofile, which is designed specifically for the head injured adult. The instrument is based on the model of occupational performance and on Luria's model of cerebral and motor functioning. It divides the concept of activities of daily living (ADL) into 3 dimensions: personal environment, home environment and community environment. It further delineates a number of activities, tasks and operations under each of these dimensions. The article presents a rationale for the instrument's development, a description of the development process and the preliminary validation work, and details of the instrument itself.

Les traumatismes crâniens constituent une cause majeure d'handicaps a long terme. Ceux-ci sont en grande partie associes aux sequelles psychologiques multiples de l'atteinte encephalique. Les travaux recents ont fourni une description des processus neuropathologiques en cause ainsi qu'une meilleure comprehension des principales sequelles psychologiques d'un traumatisme crânien grave et leurs repercussions sur l'autonomie des personnes qui en sont atteintes

We present data regarding word production and short-term auditory verbal memory in a patient, RL, who falls into the class of “reproduction conduction aphasia”. RL shows similar disturbances of single word production in naming, repetition, and reading aloud. He shows qualitatively similar and quantitatively worse performance in repetition of nonwords. His STM is good on tasks (pointing and recognition) which do not require verbal output. We conclude that his disturbance lies at a stage of word production, rather than in the process of perception or in the transfer of perceived representations to motor planning processes. We discuss existing models of the deficit in conduction aphasia and models of word recognition and production in the light of RL's performance, and we argue that none can account for the pattern of his results. We suggest that a model which incorporates two stages of phonological representations, in accordance with contemporary linguistic theory, is supported by the pattern of RL...

Referring to bicommissural coordinates, 10 human brains fixed within their own skull were examined for right-left differences of the posterior Sylvian cortex, a region known to bear the most striking gross anatomical asymmetries. In the first part of the study a millimetric assessment of right-left differences in this region was carried out using life-size lateral photographs of each hemisphere. The second part is more specifically devoted to CT recognition of these cortical areas: Each hemisphere was cut into horizontal, frontal, or sagittal slices in which some cortical landmarks were analyzed to allow accurate CT identification of gyri and sulci showing the most asymmetrical features. This work provides an anatomical framework for correlative studies dealing with cerebral dominance.

The existence of individual variations in size and shape of the human brain constitutes a problem for the anatomical interpretation of brain reconstructed images obtained from scanning devices; it is, for example, responsible for most of the inaccuracies in reading CT scans. One way to account for these variations is to use a proportional localization system. In the 1960s a group of neurosurgeons developed such a system based on two pivotal intracerebral structures, the anterior and the posterior commissures; they published an atlas consisting of horizontal, coronal, and sagittal brain sections interpreted in the proportional system. The atlas also included standard proportional brain schemas based on anatomical and radiological studies on large numbers of individuals. In this article we report a target localization experiment that we carried out to determine if this atlas could be used as a reference for a more accurate interpretation of CT and, eventually, of positron emission tomography (PET) and nuclear magnetic resonance (NMR) scans. Ten radiopaque small targets were inserted through the skull in the cortex of three cadavers; head CT was performed, and the atlas was used for predicting the cortical location of the targets seen on the CT images: The predictions were confirmed. These results strongly support the use of the proportional atlas for the interpretation of CT as well as of PET and NMR scans. Index Terms: Brain, anatomy-Atlases–Image reconstruction-Localization–Computed tomography–Nuclear magnetic resonance–Emission computed tomography.

We present data regarding assignment of thematic roles to noun phrases by RL, a reproduction conduction aphasic, in semantically reversible sentences with a variety of syntactic structures. RL makes systematic errors in sentence interpretation. With auditory presentation of sentences, he has difficulty with sentences containing relative clauses in subject position. This is consistent with his having difficulty due to a high local memory load imposed by these structures. With written presentation, RL does not distinguish three sentence types which contain the sequence NP-V-NP-V-NP. His pattern of results suggests that he does not recognise that verbs are embedded or conjoined in the sentence types in question. This may reflect the absence of prosodic cues to syntactic structure in written material. In both modalities, RL has some difficulty with passive morphology, but distinguishes passive from active sentences. The pattern of results with auditory presentation suggests that memory stores and str...

Different varieties of deviant spoken language segments (phonemic, morphemic, verbal, and syntagmic paraphasias and telescopages, neologisms) and different forms of deviant spoken language behaviors (thematic production, dyssyntaxia, glossolalia, and glossomania) are defined and exemplified. Their production is shown to be rule-governed at phonetic and phonological levels; it is shown to be rule-governed or rule-deviant at morphological and/or syntactic levels. Their qualitative and quantitative attributes in normal discourse in the jargonaphasias and in schizophasia are compared. It is underlined that the latter is a behavior episodically observed in only a small proportion of subjects considered to be schizophrenics. Awareness of, and deliberateness in, deviant language production are discussed. A distinction is made between deviations testifying to diminished ability, which betray the speaker's intention, and deviations testifying to singular but rigorous use of ability, which are adapted to the speaker's intentions. The former are contended to be common in the jargonaphasias and occasional in standard discourse and schizophasia, the latter to be characteristic of schizophasia and of various forms of “literary” language, but incompatible with aphasia. In lapidary terms, this implies that ordinary speakers think and talk standard, that (most) jargonaphasic speakers think standard but talk deviant, that schizophasic speakers think quaint and talk accordingly. It is further suggested that the differential diagnosis of jargonaphasia and schizophasia, when made on the sole basis of tape recorded samples of discursive language, resorts mainly to quantitative appraisal of different types of deviant segments on one hand, and, on the other, to the listener's interpretations of the speaker's mode of ideation. Within the realm of pathological language production, nearly exclusive and important production of phonemic transformations is said to be characteristic of conduction aphasia; combined production of numerous phonemic and verbal transformations, and of neologisms, is said to be characteristic of Wernicke's aphasia proper; nearly exclusive and important production of verbal transformations is said to be possible in so-called transcortical sensory aphasia; and predominant production of morphemic transformations and of glossomaniac utterances is said to be characteristic of schizophasia. Linguistic definitions of the “disturbances” behind schizophasic utterances are reviewed. Indications are given concerning the evolution of language behavior in jargonaphasia and schizophasia.

We have studied the frequency of exceptions to classical aphasia localizations in right-handed, literate, adult, native speakers of Italian with focal vascular left-hemisphere lesions, correlating clinical and computerized tomography data. Two hundred sixty-seven subjects were given computerized tomography (CT) examinations; lesions were mapped onto lateral diagrams and the sites of the lesions were defined. Patients were then classified as nonfluent aphasics, fluent aphasics, and nonaphasics. Patients with negative CT scans (n = 10) or only "deep" lesions (n = 50) were not studied for anatomoclinical correlations. Of the remaining 207 patients, 36 presented unexpected findings. There were seven cases of fluent aphasia and "anterior" CT lesions and six cases with nonfluent aphasia and "posterior" CT lesions among them. The significance of these findings is discussed.