Graphical Tasks to Measure Upper Limb Function in Patients With Parkinson's Disease:Validity and Response to Dopaminergic Medication

The most widely used method to assess motor functioning in Parkinson's disease (PD) patients is the unified Parkinson's disease rating scale-III (UPDRS-III). The UPDRS-III has limited ability to detect subtle changes in motor symptoms. Alternatively, graphical tasks can be used to provide objective measures of upper limb motor dysfunction. This study investigated the validity of such graphical tasks to assess upper limb function in PD patients and their ability to detect subtle changes in performance. Fourteen PD patients performed graphical tasks before and after taking dopaminergic medication. Graphical tasks included figure tracing, writing, and a modified Fitts' task. The Purdue pegboard test was performed to validate these graphical tasks. Movement time (MT), writing size, and the presence of tremor were assessed. MT on the graphical tasks correlated significantly with performance on the Purdue pegboard test (Spearman's rho > 0.65; p <0.05). MT decreased significantly after the intake of dopaminergic medication. Tremor power decreased after taking dopaminergic medication in most PD patients who suffered from tremor. Writing size did not correlate with performance on the Purdue pegboard test, nor did it change after taking medication. Our set of graphical tasks is valid to assess upper limb function in PD patients. MT proved to be the most useful measure for this purpose. The response on dopaminergic medication was optimally reflected by an improved MT on the graphical tasks in combination with a decreased tremor power, whereas writing size did not respond to dopaminergic treatment

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Sphingomyelin is associated with kidney disease in type 1 diabetes (The FinnDiane Study)

Diabetic kidney disease, diagnosed by urinary albumin excretion rate (AER), is a critical symptom of chronic vascular injury in diabetes, and is associated with dyslipidemia and increased mortality. We investigated serum lipids in 326 subjects with type 1 diabetes: 56% of patients had normal AER, 17% had microalbuminuria (20 ≤ AER < 200 μg/min or 30 ≤ AER < 300 mg/24 h) and 26% had overt kidney disease (macroalbuminuria AER ≥ 200 μg/min or AER ≥ 300 mg/24 h). Lipoprotein subclass lipids and low-molecular-weight metabolites were quantified from native serum, and individual lipid species from the lipid extract of the native sample, using a proton NMR metabonomics platform. Sphingomyelin (odds ratio 2.53, P < 10−7), large VLDL cholesterol (odds ratio 2.36, P < 10−10), total triglycerides (odds ratio 1.88, P < 10−6), omega-9 and saturated fatty acids (odds ratio 1.82, P < 10−5), glucose disposal rate (odds ratio 0.44, P < 10−9), large HDL cholesterol (odds ratio 0.39, P < 10−9) and glomerular filtration rate (odds ratio 0.19, P < 10−10) were associated with kidney disease. No associations were found for polyunsaturated fatty acids or phospholipids. Sphingomyelin was a significant regressor of urinary albumin (P < 0.0001) in multivariate analysis with kidney function, glycemic control, body mass, blood pressure, triglycerides and HDL cholesterol. Kidney injury, sphingolipids and excess fatty acids have been linked in animal models—our exploratory approach provides independent support for this relationship in human patients with diabetes

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Standardized handwriting to assess bradykinesia, micrographia and tremor in Parkinson's disease

To assess whether standardized handwriting can provide quantitative measures to distinguish patients diagnosed with Parkinson's disease from age- and gender-matched healthy control participants.  Exploratory study. Pen tip trajectories were recorded during circle, spiral and line drawing and repeated character 'elelelel' and sentence writing, performed by Parkinson patients and healthy control participants. Parkinson patients were tested after overnight withdrawal of anti-Parkinsonian medication.  University Medical Center Groningen, tertiary care, the Netherlands.  Patients with Parkinson's disease (n = 10; mean age 69.0 years; 6 male) and healthy controls (n = 10; mean age 68.1 years; 6 male).  Movement time and velocity to detect bradykinesia and the size of writing to detect micrographia. A rest recording to investigate the presence of a rest-tremor, by frequency analysis.  Mean disease duration in the Parkinson group was 4.4 years and the patients were in modified Hoehn-Yahr stages 1-2.5. In general, Parkinson patients were slower than healthy control participants. Median time per repetition, median velocity and median acceleration of the sentence task and median velocity of the elel task differed significantly between Parkinson patients and healthy control participants (all p<0.0014). Parkinson patients also wrote smaller than healthy control participants and the width of the 'e' in the elel task was significantly smaller in Parkinson patients compared to healthy control participants (p<0.0014). A rest-tremor was detected in the three patients who were clinically assessed as having rest-tremor.  This study shows that standardized handwriting can provide objective measures for bradykinesia, tremor and micrographia to distinguish Parkinson patients from healthy control participants

Reproducibility of standardized fine motor control tasks and age effects in healthy adults

Graphical tasks can provide objective measures of important motor symptoms of movement disorders such as Parkinson's disease (PD). These tasks could potentially be useful in clinical settings for (early) diagnosis and monitoring of such diseases. However, before such tasks can be used clinically, reproducibility needs to be investigated. The present study assesses the reproducibility of these graphical tasks including age-effects in healthy adults. Overall, performance on circle, spiral and zigzag tracing tasks and a writing task showed good reproducibility (intraclass correlation coefficients (ICC) > 0.7). Reproducibility was similar to the reproducibility of the Purdue pegboard task, which is an already validated fine motor control task. Reproducibility for the modified Fitts' task was moderate (ICC = 0.6). Reproducibility was higher in older participants compared to younger participants. To conclude, performance on graphical tasks, especially tracing and writing tasks, was reproducible in healthy adults, which is essential for future diagnostic and monitoring purposes in patients

Automatic MRI Quantifying Methods in Behavioral-Variant Frontotemporal Dementia Diagnosis

Aims: We assessed the value of automated MRI quantification methods in the differential diagnosis of behavioral-variant frontotemporal dementia (bvFTD) from Alzheimer disease (AD), Lewy body dementia (LBD), and subjective memory complaints (SMC). We also examined the role of the C9ORF72-related genetic status in the differentiation sensitivity. Methods: The MRI scans of 50 patients with bvFTD (17 C9ORF72 expansion carriers) were analyzed using 6 quantification methods as follows: voxel-based morphometry (VBM), tensor-based morphometry, volumetry (VOL), manifold learning, grading, and white-matter hyperintensities. Each patient was then individually compared to an independent reference group in order to attain diagnostic suggestions. Results: Only VBM and VOL showed utility in correctly identifying bvFTD from our set of data. The overall classification sensitivity of bvFTD with VOL + VBM achieved a total sensitivity of 60%. Using VOL + VBM, 32% were misclassified as having LBD. There was a trend of higher values for classification sensitivity of the C9ORF72 expansion carriers than noncarriers. Conclusion: VOL, VBM, and their combination are effective in differential diagnostics between bvFTD and AD or SMC. However, MRI atrophy profiles for bvFTD and LBD are too similar for a reliable differentiation with the quantification methods tested in this study