Age-related changes in the bimanual advantage and in brain oscillatory activity during tapping movements suggest a decline in processing sensory reafference

Deficits in the processing of sensory reafferences have been suggested as accounting for age-related decline in motor coordination. Whether sensory reafferences are accurately processed can be assessed based on the bimanual advantage in tapping: because of tapping with an additional hand increases kinesthetic reafferences, bimanual tapping is characterized by a reduced inter-tap interval variability than unimanual tapping. A suppression of the bimanual advantage would thus indicate a deficit in sensory reafference. We tested whether elderly indeed show a reduced bimanual advantage by measuring unimanual (UM) and bimanual (BM) self-paced tapping performance in groups of young (n = 29) and old (n = 27) healthy adults. Electroencephalogram was recorded to assess the underlying patterns of oscillatory activity, a neurophysiological mechanism advanced to support the integration of sensory reafferences. Behaviorally, there was a significant interaction between the factors tapping condition and age group at the level of the inter-tap interval variability, driven by a lower variability in BM than UM tapping in the young, but not in the elderly group. This result indicates that in self-paced tapping, the bimanual advantage is absent in elderly. Electrophysiological results revealed an interaction between tapping condition and age group on low beta band (14–20 Hz) activity. Beta activity varied depending on the tapping condition in the elderly but not in the young group. Source estimations localized this effect within left superior parietal and left occipital areas. We interpret our results in terms of engagement of different mechanisms in the elderly depending on the tapping mode: a ‘kinesthetic’ mechanism for UM and a ‘visual imagery’ mechanism for BM tapping movement.     

The Complex Intratumoral Heterogeneity of Colon Cancer Highlighted by Laser Microdissection

Aims  

To evaluate the utility of laser microdissection in the comparison of phenotypes and genetic alterations between colon cancer and corresponding liver metastasis in the context of intratumoral heterogeneity.     

Bortezomib combined with low-dose cytarabine in Intermediate-2 and high risk myelodysplastic syndromes. A phase I/II Study by the GFM

Marrow cells from patients with higher-risk myelodysplastic syndrome (MDS) exhibit constitutive nuclear factor (NF)-κB activation. The proteasome inhibitor, bortezomib, has limited efficacy as a single agent in acute myeloid leukaemia. Its activity on leukaemic cell lines is potentiated by chemotherapy. We treated 43 higher-risk MDS patients with bortezomib (1·5 mg/m(2) , days 1, 4, 8 and 11) and low dose cytarabine arabinoside (LDAC; 10 mg/m(2) , then 20 mg/m(2) from days 1-14), every 28 d for four cycles. Median follow-up was 29·7 months. Responses were seen in 12 of the 43 patients (28%), including complete response (CR, n = 1), marrow-CR (n = 3), partial response (PR, n = 5) and haematological improvement (HI, n = 3). Responses were seen in 12 (36%) of the 33 previously untreated patients (11% CR, 13% PR, 2·5% HI), compared to none in the 12 previously treated patients (P < 0·01). Responders had better overall survival (median 18·2 vs. 10 months). One CR and 3 marrow-CRs were seen in patients with complex karyotypes. Main toxicity was haematological, responsible for infection in six patients and bleeding in 3. Three patients with Grade 1-2 pre-treatment haematotoxicity developed Grade 3-4 toxicity. Neuropathy was seen in 12% of patients. The addition of bortezomib to LDAC in higher-risk MDS may improve results obtained with LDAC alone, especially in patients with unfavourable karyotypes.     

Accuracy and disagreement of computed tomography and magnetic resonance imaging for the diagnosis of small hepatocellular carcinoma and dysplastic nodules: role of biopsy

Liver macronodules, ranging from benign to low-grade or high-grade dysplastic nodules (LGDNs/HGDNs) and hepatocellular carcinoma (HCC), may develop during chronic liver diseases (CLDs). Current guidelines were recently updated and the noninvasive criteria for the diagnosis of small HCC are based on a single typical radiological pattern and nonconclusive coincidental findings with two techniques. This study aimed to assess the accuracy and disagreements of noninvasive multiphasic examinations for the diagnosis of HCC and dysplastic nodules (DNs) and the role of biopsy. Seventy-four consecutive patients with CLD with ultrasound-detected 1-2-cm nodules underwent, within 1 month, multiphasic computed tomography (CT), magnetic resonance imaging (MRI), and biopsy of the nodule. Median age was 60 years; 33 patients (45%) had hepatitis C virus, 20 (27%) had hepatitis B virus, and 13 (18%) patients had no cirrhosis. Biopsy revealed 47 HCCs, 6 HGDNs, 1 LGDNs, 1 cholangiocarcinoma, and 1 epithelioid hemangioendothelioma. There were no tumors in the other 18 patients. All patients (31 of 31; 100%) who had conclusive coincidental findings (i.e., arterial enhancement and washout) on both examinations had HCC or HGDN (sensitivity, 57%; specificity, 100%). All patients (51 of 51; 100%) who had conclusive findings on at least one of the two examinations had HCC or HGDN (sensitivity, 96%; specificity, 100%). There was a disagreement regarding imaging findings between CT and MRI in 21 of 74 (28%) patients and no washout on both examinations in 23 of 74 patients (31%). In these 44 patients, liver biopsy provided an initial accurate diagnosis. CONCLUSION: The noninvasive diagnosis of HCC or HGDN can be obtained if arterial enhancement and washout are found in a single dynamic imaging examination. These findings are frequently discordant on both CT and MRI, supporting the place of biopsy for the diagnosis of small HCCs.     

The Isolation of Numerals at the Semantic Level

Abstract

In this study, we examine the case of a patient (NM) who could comprehend and produce numerals despite impairment on comprehension tasks and a high degree of anomia for other categories of words. It will be claimed that NM suffered from an impairment to the semantic system affecting all categories except numerals and the series of days and months. The case of a patient presenting with the exact reverse dissociation has been described a few years ago by Cipolotti et al. (Brain 1991; 114: 619–37). We conclude that NM's pattern of performance provides evidence that numerals constitute a relevant and perhaps a distinct category at the semantic level.     

Neuropathological features in a female fetus with OPHN1 deletion and cerebellar hypoplasia

We report the case of a 33-year-old pregnant woman. The third-trimester ultrasound scan during pregnancy revealed fetal bilateral ventricular dilatation, macrosomia and a transverse diameter of the cerebellum at the 30th centile. A brain MRI scan at 31 weeks of gestation led to a diagnosis of hypoplasia of the cerebellar vermis without hemisphere abnormalities and a non compressive expansion of the cisterna magna. The fetal karyotype was 46,XX. The pregnancy was terminated and array-CGH analysis of the fetus identified a 238 kb de novo deletion on chromosome Xp12, encompassing part of OPHN1 gene. Further studies revealed a completely skewed pattern of X inactivation. OPHN1 is involved in X-linked mental retardation (XLMR) with cerebellar hypoplasia and encodes a Rho-GTPase-activating protein called oligophrenin-1, which is produced throughout the developing mouse brain and in the hippocampus and Purkinje cells of the cerebellum in adult mice. Neuropathological examination of the female fetus revealed cerebellar hypoplasia and the heterotopia of Purkinje cells at multiple sites in the white matter of the cerebellum. This condition mostly affects male fetuses in humans. We report here the first case of a de novo partial deletion of OPHN1, with radiological and neuropathological examination, in a female fetus.     

The psychological impact of cryptic chromosomal abnormalities diagnosis announcement

This qualitative study aims to describe the psychological impact of the diagnosis announcement of pathogenic Copy Number Variations (pCNVs). We performed semi-structured interviews of 60 parents of 41 affected children and 5 geneticists who announced the diagnoses. The diagnosis of the best characterized microdeletion syndromes, often defined by patronymic names (e.g. Williams syndrome), is generally made on a clinical basis by geneticists and confirmed by fluorescence in situ hybridization analysis. Chromosomal microarray, on the contrary, can allow the disclosure of rare pCNVs named after cytogenetic formulas, with poorly known clinical consequences: this makes doctors feel less confident with these diagnosis announcements. The disclosure of pCNVs named after cytogenetic formulas does not facilitate the parental mental representation of the disease, leading some parents to call into question the genotype-phenotype correlation or the very notion of a diagnosis. The announcement of inherited pCNVs can increase the feeling of parental guilt; the disclosure of de novo pCNVs can induce a feeling of “breakage” in the mental representation of the parent-child vertical transmission. In conclusion, our study shows that the disclosure of pCNVs has a significant psychological impact: a multidisciplinary approach to the diagnosis announcement, including a psychological support, should be systematically warranted.     

Seasonal variations of systemic lupus erythematosus flares in southern France

ObjectiveExposure to sunlight is one of the environmental factors involved in the pathogenesis of systemic lupus erythematosus. We investigated whether there is seasonal variation in the incidence of cutaneous and noncutaneous severe lupus flares in southern France.MethodsWe retrospectively reviewed clinical and biological data from all SLE patients hospitalized for a flare of the disease during a two year period in our centre and collected corresponding meteorological data from the official website of MeteoFrance.ResultsForty one patients, mean age 36.7 ± 13.8 years, were included. Twenty-six patients (63.4%) had kidney biopsy performed, showing in all cases proliferative nephritis, associated with membranous nephritis in 9 (22%). We found a clear seasonal pattern for overall lupus flares with 39% of flares occurred in Spring. Among patients without any cutaneous involvement, this seasonal pattern was still observed (p = 0.024). Patients under antimalarials presented flares significantly later in the sunny season than those without (respectively median in July versus May, p = 0.044). There were strong positive correlations between occurrence of lupus flares and maximum temperature increase (ρ = 0.87, p < 0.001), minimum temperature increase (ρ = 0.87, p < 0.001), and duration of sunshine increase (ρ = 0.78, p = 0.003). These correlations were also observed in patients with renal flares.ConclusionWe confirmed a seasonal pattern for lupus flares among patients living in Southern France, with most flares in spring, in correlation with an increase in temperature and duration of sunshine. A similar seasonal pattern was observed in patients with no cutaneous involvement and with visceral involvement.