Microstructural changes in white matter associated with freezing of gait in Parkinson's disease

In Parkinson's disease (PD), freezing of gait (FOG) is associated with widespread functional and structural gray matter changes throughout the brain. Previous study of freezing‐related white matter changes was restricted to brainstem and cerebellar locomotor tracts. This study was undertaken to determine the spatial distribution of white matter damage associated with FOG by combining whole brain and striatofrontal seed‐based diffusion tensor imaging. Diffusion‐weighted images were collected in 26 PD patients and 16 age‐matched controls. Parkinson's disease groups with (n = 11) and without freezing of gait (n = 15) were matched for age and disease severity. We applied tract‐based spatial statistics to compare fractional anisotropy and mean diffusivity of white matter structure across the whole brain between groups. Probabilistic tractography was used to evaluate fractional anisotropy and mean diffusivity of key subcortico‐cortical tracts. Tract‐based spatial statistics revealed decreased fractional anisotropy in PD with FOG in bilateral cerebellar and superior longitudinal fascicle clusters. Increased mean diffusivity values were apparent in the right internal capsule, superior frontal cortex, anterior corona radiata, the left anterior thalamic radiation, and cerebellum. Tractography showed consistent white matter alterations in striatofrontal tracts through the putamen, caudate, pallidum, subthalamic nucleus, and in connections of the cerebellar peduncle with subthalamic nucleus and pedunculopontine nucleus bilaterally. We conclude that FOG is associated with diffuse white matter damage involving major cortico‐cortical, corticofugal motor, and several striatofrontal tracts in addition to previously described cerebello‐pontine connectivity changes. These distributed white matter abnormalities may contribute to the motor and non‐motor correlates of FOG. © 2015 International Parkinson and Movement Disorder Society     

Regional volumes in brain stem and cerebellum are associated with postural impairments in young brain‐injured patients

Many patients with traumatic brain injury (TBI) suffer from postural control impairments that can profoundly affect daily life. The cerebellum and brain stem are crucial for the neural control of posture and have been shown to be vulnerable to primary and secondary structural consequences of TBI. The aim of this study was to investigate whether morphometric differences in the brain stem and cerebellum can account for impairments in static and dynamic postural control in TBI. TBI patients (n = 18) and healthy controls (n = 30) completed three challenging postural control tasks on the EquiTest® system (Neurocom). Infratentorial grey matter (GM) and white matter (WM) volumes were analyzed with cerebellum‐optimized voxel‐based morphometry using the spatially unbiased infratentorial toolbox. Volume loss in TBI patients was revealed in global cerebellar GM, global infratentorial WM, middle cerebellar peduncles, pons and midbrain. In the TBI group and across both groups, lower postural control performance was associated with reduced GM volume in the vermal/paravermal regions of lobules I–IV, V and VI. Moreover, across all participants, worse postural control performance was associated with lower WM volume in the pons, medulla, midbrain, superior and middle cerebellar peduncles and cerebellum. This is the first study in TBI patients to demonstrate an association between postural impairments and reduced volume in specific infratentorial brain areas. Volumetric measures of the brain stem and cerebellum may be valuable prognostic markers of the chronic neural pathology, which complicates rehabilitation of postural control in TBI. Hum Brain Mapp 36:4897–4909, 2015. © 2015 Wiley Periodicals, Inc.     

Predictors of CD4+ cell count response and of adverse outcome among HIV-infected patients receiving highly active antiretroviral therapy in a public hospital in Peru.

OBJECTIVES: Our aim was to investigate CD4+ cell recovery and adverse outcome after highly active antiretroviral therapy (HAART) under the Peruvian National Program for HIV. METHODS: A prospective, observational study was conducted between May 2004 and September 2005. Data were collected from records of patients receiving HAART at a public hospital under the Peruvian National Program for HIV. Predictors of CD4+ cell count recovery and adverse outcome were analyzed by multiple regression. RESULTS: Three hundred and twenty-six patients were included in the study. The mean increase in CD4+ cell count at six months was 114 cells/microl (95% confidence interval: 103-126). Patients with a lower CD4+ cell count at baseline and those starting HAART with a didanosine-based regimen had a higher increase in CD4+ cell count at six months. Patients starting HAART with a stavudine-based regimen had a lower increase in CD4+ cell count at six months. World Health Organization clinical stage IV at diagnosis of HIV infection, a low body weight at baseline, and starting HAART with a stavudine-based regimen were independently associated with an adverse outcome. CONCLUSIONS: The CD4+ cell response to HAART under Peruvian National Program for HIV was comparable with reports from other countries. However, the fact that advanced clinical disease predicted adverse outcome emphasizes the need for earlier access to HAART.     

Plasma adiponectin level is inversely correlated with albuminuria in overweight and obese nondiabetic individuals

ObjectiveTo explore the relationship between adiponectin and albuminuria in a large group of overweight and obese nondiabetic individuals after controlling for potential confounders.Material and MethodsDetailed anthropometry, computed tomography-measured visceral abdominal adipose tissue, 24-h albuminuria, adiponectin and a series of biochemical parameters were assessed. Four hundred forty patients, predominantly of Caucasian origin, were included (80.2% female). A multiple linear regression model was developed, with albuminuria as the dependent variable and potential predictors as independent variables.ResultsThe mean age was 40 ± 13 years, the mean body mass index was 35.7 ± 6.6 kg/m², and the median visceral abdominal adipose tissue was 142.4 (92.3–194.0) cm². 10.9% of subjects exhibited microalbuminuria. The median adiponectin level was 9.08 (6.23–12.94) μg/ml, and the median fasting serum glucose level was 83 (77–89) mg/dl. The strongest significant univariate correlations with albuminuria were visceral abdominal adipose tissue (r = 0.258, p < 0.001), adiponectin (r = ? 0.265, p < 0.001), waist circumference (r = 0.250, p < 0.001), waist-to-hip ratio (r = 0.236, p < 0.001) and high-density lipoprotein cholesterol (r = ? 0.211, p < 0.001). The multiple linear regression model revealed a significant positive independent correlation between visceral abdominal adipose tissue and albuminuria (r = 0.134, p = 0.033), between fasting glucose levels and albuminuria (r = 0.390, p = 0.029) and between gender and albuminuria (r = 0.107, p = 0.038). A significant independent negative correlation was identified between adiponectin and albuminuria (r = ? 0.255, p = 0.022).ConclusionsWe observed an independent inverse relationship between adiponectin and albuminuria in overweight and obese nondiabetic individuals. Further investigations are needed to confirm this finding and to clarify whether adiponectin is a risk marker or plays a causative role in developing obesity-induced nephropathy.     

Seroprotection against tetanus in patients attending an emergency department in Belgium and evaluation of a bedside immunotest.

BACKGROUND: In most emergency departments, tetanus prophylaxis currently relies on vaccination history. Bedside evaluation of tetanus immunity may improve this process. OBJECTIVES: (i) To determine the seroprevalence of tetanus immunity; (ii) to evaluate the accuracy of vaccination history in assessing tetanus immunity; (iii) to identify factors predictive of seroprotection and incorrect history. METHOD: In a prospective observational study, tetanus immunity was assessed in 784 adults using Tétanos Quick Stick (TQS). A questionnaire was completed to obtain vaccination and general histories. Immunity assessed by TQS and by vaccination history were compared with anti-tetanus antibody levels measured by the enzyme-linked immunosorbent assay (seroprotection threshold >0.15 IU/ml). RESULTS: Overall, 64.2% of patients were protected according to TQS results. Four independent predictors of seroprotection were identified: young age, birthplace in Belgium, male sex and occupational medicine consultation. TQS performance was good: kappa=0.71, sensitivity 85.3%, specificity 87.2%, positive predictive value 92.1% and negative predictive value 77.2%. Seven hundred and sixty-two participants responded to the vaccination history: 23.4% said they were protected, 22.1% that they were not and 54.5% did not know. History performance was poor: kappa=0.27, sensitivity 60.3%, specificity 73.3%, positive predictive value 81.8% and negative predictive value 45.8%. Compared with history, TQS offered a significantly better sensitivity, negative and positive predictive values, but specificity was similar. No predictor of an incorrect history was identified. CONCLUSION: Lack of protective immunity against tetanus is frequent but poorly evaluated by history taking. Several demographic characteristics are good predictors of seroprotection. TQS could be a valuable tool in selected patients to improve tetanus prophylaxis in the emergency department.     

Between-limb asynchronies during bimanual coordination: Effects of manual dominance and attentional cueing

Whereas previous studies on interlimb coordination have mainly underscored the ubiquitous tendency to synchronize the motions of the limbs, the present experiment revealed a small, but distinct, interlimb asynchrony or phase offset, i.e. the dominant limb led the non-dominant limb during the production of bimanual circle drawing. This asynchrony was clearly evident in the majority of right-handers, but not in left-handers. Moreover, attentional cueing affected the size of the asynchrony. Instructions to visually monitor the dominant limb or non-dominant limb strengthened and weakened the phase offset, respectively. A multifactorial neural account is proposed to underly the temporal asynchrony.     

Stromal cells from the rat prostate secrete androgen-regulated factors which modulate Sertoli cell function

Testicular peritubular cells produce paracrine mediators which modulate Sertoli cell function. The production of these mediators (P Mod-S) is controlled by androgens suggesting that mesenchymal-epithelial interactions play an important role in androgen action in the testis. We investigated whether mesenchymal cells from the prostate, another androgen target tissue, produce analogous mediators. To this end rat Sertoli cell cultures were exposed to dialyzed spent media derived from testicular peritubular cells, prostatic stromal cells or footsole fibroblasts. It is demonstrated that the effects of spent media from peritubular cells and stromal cells are nearly identical: they stimulate the production of androgen binding protein and transferrin and they inhibit FSH-inducible aromatase activity. The active principle (or principles) involved is non-dialyzable, heat sensitive and trypsin sensitive. Its production is markedly stimulated by androgens. Fibroblast spent media are inactive. It is concluded that mesenchymal tissue derived from different androgen target tissues may produce identical or similar mediators of androgen action acting on epithelial cells.     

High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic oligodendroglioma: long-term follow-up

We previously reported a phase 2 trial of 69 patients with newly diagnosed anaplastic or aggressive oligodendroglioma who were treated with intensive procarbazine, CCNU (lomustine), and vincristine (PCV) followed by high-dose thiotepa with autologous stem cell rescue. This report summarizes the long-term follow-up of the cohort of 39 patients who received high-dose thiotepa with autologous stem cell support. Thirty-nine patients with a median age of 43 (range, 18-67) and a median KPS of 100 (range, 70-100) were treated. Surviving patients now have a median follow-up of 80.5 months (range, 44-142). The median progression-free survival is 78 months, and median overall survival has not been reached. Eighteen patients (46%) have relapsed. Neither histology nor prior low-grade oligodendroglioma correlated with risk of relapse. Persistent nonenhancing tumor at transplant was identified in our initial report as a significant risk factor for relapse; however, long-term follow-up has not confirmed this finding. Long-term neurotoxicity has developed only in those patients whose disease relapsed and required additional therapy; no patient in continuous remission has developed a delayed neurologic injury. This treatment strategy affords long-term disease control to a subset of patients with newly diagnosed anaplastic oligodendroglioma without evidence of delayed neurotoxicity or myelodysplasia.