Early Parkinson's disease: Longitudinal changes in brain activity during sequence learning

Impairment of sequence learning is common in Parkinson's disease (PD), but the time course of this cognitive abnormality is not known. We assessed longitudinal changes in sequence learning performance and associated task-related cerebral blood flow in 13 early stage PD patients who underwent H₂¹⁵O PET at baseline and again 2 years later. Ten healthy volunteer subjects served as controls. A trend toward decline in learning performance (p = 0.08) was evident over the 2 years of follow-up. During this interval, significant declines in learning-related activation were detected in parietal and temporo-occipital association areas and in the right dorsolateral prefrontal cortex. Learning-related activation in these regions was normal at baseline, but declined to subnormal levels (p < 0.01) at 2 years. Significant hippocampal activation (p < 0.005) was present in the subjects with high learning performance over time. The findings are consistent with a decline in learning-related neural activity in cortical areas with prominent Lewy body formation.     

Genetic prion disease with codon 196 PRNP mutation: clinical and pathological findings

Ten percent to 15% of all human transmissible spongiform encephalopathy are characterized by a mutation in prion protein gene (PRNP). They are distinct with respect to clinical signs, disease onset, disease duration, and diagnostic findings. During our surveillance activities in Germany, we identified 7 patients with the rare mutation E196K in PRNP gene, thereof 4 patients belonging to 2 families. The clinical syndromes were characterized by nonspecific and psychiatric symptoms at disease onset and progressed to predominant motor signs. These patients showed a late median disease onset of 71 years and short disease duration of 6.5 months. In absence of family history, they mimicked sporadic Creutzfeldt-Jakob disease (CJD). In clinical tests they were 100% positive for 14-3-3 protein detection in cerebrospinal fluid and less sensitive for magnetic resonance imaging (MRI) and electroencephalogram (EEG) abnormalities. As a secondary magnetic resonance imaging (MRI) abnormality, we have seen conspicuous common involvement of the subcortical white matter in 57%. Four patients underwent autopsy—pathological lesions revealed striking similarity to sporadic Creutzfeldt-Jakob disease but also involvement of the white matter.     

Leptin signalling and leptin-mediated activation of human platelets: importance of JAK2 and the phospholipases Cgamma2 and A2

Leptin enhances agonist-induced platelet aggregation, and human platelets have been reported to express the leptin receptor. However, the pathways and mediators lying downstream of leptin binding to platelets remain, with few exceptions, unknown. In the present study, we sought to gain further insight into the possible role of leptin as a platelet agonist. Stimulation of platelets with leptin promoted thromboxane generation and activation of alpha(IIb)beta(3), as demonstrated by PAC-1 binding. Furthermore, it increased the adhesion to immobilised fibrinogen (p<0.001) and induced cytoskeletal rearrangement of both platelets and Meg01 cells. Leptin time- and dose-dependently phosphorylated the intracellular signalling molecules JAK2 and STAT3, although the importance of STAT3 for leptin-induced platelet activation remains to be determined. Important intracellular mediators and pathways activated by leptin downstream of JAK2 were found to include phosphatidylinositol-3 kinase, phospholipase Cgamma2 and protein kinase C, as well as the p38 MAP kinase-phospholipase A(2) axis. Accordingly, incubation with the specific inhibitors AG490, Ly294002, U73122, and SB203580 prevented leptin-mediated platelet activation. These results help delineate biologically relevant leptin signalling pathways in platelets and may improve our understanding of the mechanisms linking hyperleptinaemia to the increased thrombosis risk in human obesity.     

Neural correlates of trust

Trust is a critical social process that helps us to cooperate with others and is present to some degree in all human interaction. However, the underlying brain mechanisms of conditional and unconditional trust in social reciprocal exchange are still obscure. Here, we used hyperfunctional magnetic resonance imaging, in which two strangers interacted online with one another in a sequential reciprocal trust game while their brains were simultaneously scanned. By designing a nonanonymous, alternating multiround game, trust became bidirectional, and we were able to quantify partnership building and maintenance. Using within- and between-brain analyses, an examination of functional brain activity supports the hypothesis that the preferential activation of different neuronal systems implements these two trust strategies. We show that the paracingulate cortex is critically involved in building a trust relationship by inferring another person's intentions to predict subsequent behavior. This more recently evolved brain region can be differently engaged to interact with more primitive neural systems in maintaining conditional and unconditional trust in a partnership. Conditional trust selectively activated the ventral tegmental area, a region linked to the evaluation of expected and realized reward, whereas unconditional trust selectively activated the septal area, a region linked to social attachment behavior. The interplay of these neural systems supports reciprocal exchange that operates beyond the immediate spheres of kinship, one of the distinguishing features of the human species.     

Reliability and validity of YRBS physical activity items among middle school students

PURPOSE: To assess test-retest reliability and validity of the Youth Risk Behavior Survey (YRBS) items for moderate and vigorous physical activity in middle school students. METHODS: Students (N = 125; 12.7 +/- 0.6 yr) wore Actigraph accelerometers for 6.1 +/- 1.0 d and twice completed surveys that included YRBS moderate and vigorous physical activity items. Accelerometer counts were transformed into minutes of moderate (3-6 METs) and vigorous (> 6 METs) physical activity. Days per week meeting moderate and vigorous physical activity recommendations were estimated using four summary methods. Reliability was assessed using intraclass correlation coefficients (ICC) from the two surveys. Validity was assessed as percent concordance, kappa coefficients, and sensitivity and specificity using binary YRBS and Actigraph outcomes. RESULTS: Test-retest ICC for the moderate and vigorous physical activity items were 0.51 and 0.46, respectively. Twenty-two percent of students met the recommended level of moderate physical activity (>or= 30 min.d(-1), >or= 5 d.wk(-1)) according to self-reports, whereas 90.4 and 66.4% met the recommendation according to accumulated accelerometer minutes and 5-min-bout criteria, respectively. Concordance between YRBS and Actigraph moderate physical activity measures was highest using accumulated accelerometer minutes. Sensitivity of the moderate YRBS item ranged from 0.19 to 0.23 for four comparisons, and specificity was 0.74-0.92. More than two thirds of students reported vigorous physical activity at recommended levels (>or= 20 min.d(-1), >or= 3 d.wk(-1)), whereas the highest prevalence according to Actigraph monitoring was 22.4%. Sensitivity of the YRBS vigorous item was high (0.75-0.92) compared with the four Actigraph measures; specificity was low (0.23-0.26). CONCLUSION: YRBS questions underestimate the proportion of students attaining recommended levels of moderate physical activity and overestimate the proportion meeting vigorous recommendations. Use of accelerometry for physical activity surveillance seems to be indicated. At the minimum, new questions demonstrating greater validity are needed.     

Cardiac amyloidosis: MR imaging findings and T1 quantification, comparison with control subjects

In cardiac amyloidosis an interstitial deposition of amyloid fibrils causes concentric thickening of the atrial and ventricular walls. We describe the results of tissue characterization of the myocardium by T1 quantification and MRI findings in a patient with cardiac amyloidosis. The T1 time of the myocardium was elevated compared to that in individuals without amyloidosis. The T1 time of the myocardium was 1387 +/- 63 msec (mean value obtained from four measurements +/- standard deviation [SD]) in the patient with cardiac amyloidosis, while the reference value obtained from the myocardium of 10 individuals without known myocardial disease was 1083 +/- 33 msec (mean value +/- SD). In combination with other MR findings suggestive of amyloidosis, such as homogeneous thickening of the ventricular and atrial walls, thickening of the valve leaflets, restrictive filling pattern, and reduction of systolic function, T1 quantification may increase diagnostic confidence.     

Migration and colon perforation of intraperitoneal cardiac pacemaker systems

Epicardial pacemaker systems include pacing leads and a generator, which exceptionally may have to be implanted in the abdomen. We report three such pediatric cases where severe intraabdominal complications occurred owing to migration and erosion of the generators into visceral organs and urge extreme caution with this technique.     

Pain Sensitivity in Sleepy Pain-Free Normals

Study Objective:

Past studies have shown that acute experimental reduction of time in bed in otherwise healthy, non-sleepy people leads to hyperalgesia. We hypothesized that otherwise healthy, sleepy people may also exhibit hyperalgesia relative to their non-sleepy counterparts.

Design:

Between-groups sleep laboratory study.

Setting:

Hospital-based sleep disorders center.

Participants:

Twenty-seven, healthy, normal participants (age 18–35 years) were recruited and categorized into sleepy and non-sleepy groups based on their average sleep latencies on a screening multiple sleep latency test (MSLT).

Interventions:

Both groups were then allowed 8 hours time in bed, following which they underwent pain sensitivity testing (10:30 and 14:30) and sleepiness assessments by the MSLT (10:00, 12:00, 14:00, and 16:00). Pain sensitivity assessments were made by measuring finger withdrawal latencies to a radiant heat source delivering 5 different heat intensities.

Measurements and Results:

This study showed that after only one night of 8 hours time in bed, the sleepy participants continued to be sleepy and exhibited a more rapid finger withdrawal response (i.e., increased pain sensitivity) to radiant heat than non-sleepy participants.

Conclusion:

This suggests that sleepy individuals experience hyperalgesia in response to a painful stimulus when compared with non-sleepy individuals.

Citation:

Chhangani BS; Roehrs TA; Harris EJ; Hyde M; Drake C; Hudgel DW; Roth T. Pain sensitivity in sleepy pain-free normals. SLEEP 2009;32(8):1011-1017.