Brain injury pathophysiology study by a multimodal approach in children with sickle cell anemia with no intra or extra cranial arteriopathy

Despite its high prevalence in children with sickle cell anemia (SCA), the pathophysiology of silent cerebral infarcts (SCI) remains elusive. The main objective of this study was to explore the respective roles of major determinants of brain perfusion in SCA children with no past or current history of intracranial or extracranial vasculopathy. We used a multimodal approach based notably on perfusion imaging arterial spin labeling (ASL) magnetic resonance imaging (MRI) and near infra-red spectroscopy (NIRS), as well as biomarkers reflecting blood rheology and endothelial activation. Out of 59 SCA patients (mean age 11.4±3.9 yrs), eight (13%) had a total of 12 SCI. Children with SCI had a distinctive profile characterized by decreased blood pressure, impaired blood rheology, increased P-selectin levels, and marked anemia. Although ASL perfusion and oximetry values did not differ between groups, comparison of biological and clinical parameters according to the level of perfusion categorized in terciles showed an independent association between high perfusion and increased sP-selectin, decreased red blood cell deformability, low hemoglobin F level, increased blood viscosity and no -thalassemia deletion. NIRS measurements did not yield additional novel results. Altogether, these findings argue for early MRI detection of SCI in children with no identified vasculopathy and suggest a potential role for ASL as an additional screening tool. Early treatment targeting hemolysis, anemia and endothelial dysfunction should reduce the risk of this under diagnosed and serious complication.     

Neurological Gait Abnormalities Moderate the Functional Brain Signature of the Posture First Hypothesis

The posture first hypothesis suggests that under dual-task walking conditions older adults prioritize gait over cognitive task performance. Functional neural confirmation of this hypothesis, however, is lacking. Herein, we determined the functional neural correlates of the posture first hypothesis and hypothesized that the presence of neurological gait abnormalities (NGA) would moderate associations between brain activations, gait and cognitive performance. Using functional near-infrared spectroscopy we assessed changes in oxygenated hemoglobin levels in the pre-frontal cortex (PFC) during normal walk and walk while talk (WWT) conditions in a large cohort of non-demented older adults (n = 236; age = 75.5 ± 6.49 years; female = 51.7 %). NGA were defined as central (due to brain diseases) or peripheral (neuropathic gait) following a standardized neurological examination protocol. Double dissociations between brain activations and behavior emerged as a function of NGA. Higher oxygenation levels during WWT were related to better cognitive performance (estimate = 0.145; p < 0.001) but slower gait velocity (estimate = ?6.336, p < 0.05) among normals. In contrast, higher oxygenation levels during WWT among individuals with peripheral NGA were associated with worse cognitive performance (estimate = ?0.355; p < 0.001) but faster gait velocity (estimate = 14.855; p < 0.05). Increased activation in the PFC during locomotion may have a compensatory function that is designed to support gait among individuals with peripheral NGA.     

The relationship between hippocampal volume and static postural sway: results from the GAIT study

The role of the hippocampus in postural control, in particular in maintaining upright stance, has not been fully examined in normal aging. This study aims to examine the association of postural sway with hippocampal volume while maintaining upright stance in healthy older individuals. Seventy healthy individuals (mean age 69.7 ± 3.4 years; 41.4 % women) were recruited in this study based on cross-sectional design. Hippocampal volume (quantified from a three-dimensional T₁-weighted MRI using semi-automated software), three center of pressure (COP) motion parameters (sway area, path length of anterior-posterior (AP) and medial-lateral (ML) displacement) while maintaining upright stance (eyes open and closed), and the relative difference between open and closed eye conditions were used as outcome measures. Age, sex, body mass index, lower limb proprioception, distance vision, 15-item geriatric depression scale score, total cranial volume, and white matter abnormalities were used as covariates. The sway area decreased from open to closed eye condition but this variation was non-significant (P = 0.244), whereas path length of AP and ML displacement increased significantly (P < 0.003). Increase in sway area from open to closed eyes was associated with greater hippocampal volume (β ?18.21; P = 0.044), and a trend for an association of increase in path length of AP displacement (P = 0.075 for open eyes and P = 0.071 for closed eyes) with greater hippocampal volume was reported. The hippocampus is involved in upright postural control in normal aging, such that an increase in sway area of COP motion from open to closed eyes is associated with greater hippocampal volume in healthy older adults.     

Fraser syndrome. A case report

Fraser syndrome is a rare autosomal recessive disorder; the most consistent features are cryptophthalmos, syndactyly of fingers and toes, laryngeal stenosis, and urogenital abnormalities. We report a newborn case at day 1 of life who had multiple abnormalities, born from a consanguineous marriage. Clinically, the newborn had an ankyloblepharon on the left side, a cryptophthalmos on the right side, a syndactyly, anorectal abnormalities with ambiguous genitalia, laryngeal stenosis, and ear malformations. TDM of the cranium and orbits and the transfontanel ultrasound were normal. The abdominal ultrasound showed renal abnormalities. Right eye surgery showed a reduced cornea to an opaque thin plate clinging to the iris without an anterior chamber and a nonindividualized eyeball. The authors discuss the morphological abnormalities, the clinical and paraclinical aspects of this syndrome, its multispecialized clinical management, and the importance of prenatal diagnosis.     

BRCA1/BRCA2 Mutations Shaped by Ancient Consanguinity Practice in Southern Mediterranean Populations

The aim of this study is to investigate the involvement of consanguinity on BRCA1/2 mutation incidence in SouthernMediterranean populations and to confirm their low penetrance by comparison of their recurrence in sporadic and familialbreast cancer in a context of ancient consanguinity practice. Our study comprises of two parts: First, a comparison ofthe consanguinity rates of the South Mediterranean countries in a relationship with the frequency of BRCA1 deleteriousmutations in breast cancer families and the recurrence of these mutations. Second, we investigated 23patients with afamily history of breast cancer, 51 patients without a family history of breast cancer using next-generation sequencingof BRCA2 and then confirmed by Sanger sequencing for the novel mutation. As results, we clearly show a strongrelationship between the frequency of BRCA1 deleterious mutations in breast cancer families and rate of consanguinity,since they are significantly inversely correlated. Four deleterious mutations were found in BRCA2 gene including anovel frame-shift mutationc.9382_9383dup in a patient with familial breast cancer and three other frame-shift mutationsc.6591_6592del, c.1310_1313del and c.7654dup in patients with sporadic breast cancer.These results are discussedin a context of selective pressure of ancient consanguinity practice. In conclusion, the study of BRCA1/2 gene inSouthern Mediterranean countries revealed low penetrance recurrent mutations in sporadic and familial breast cancer.These mutations have been selected in a context of ancient consanguinity practice along with protective genetic andenvironmental factors.     

Falls,Cognitive Impairment,and Gait Performance: Results From the GOOD Initiative

Objectives

Falls are highly prevalent in individuals with cognitive decline. The complex relationship between falls and cognitive decline (including both subtype and severity of dementia) and the influence of gait disorders have not been studied. This study aimed to examine the association between the subtype (Alzheimer disease [AD] versus non-AD) and the severity (from preclinical to moderate dementia) of cognitive impairment and falls, and to establish an association between falls and gait parameters during the course of dementia.