A systematic review of biomarkers for disease progression in Parkinson's disease

Peer reviewedPublisher PD

Standardized patient outcomes trial (SPOT) in neurology

Background: The neurologic examination is a challenging component of the physical examination for medical students. In response, primarily based on expert consensus, medical schools have supplemented their curricula with standardized patient (SP) sessions that are focused on the neurologic examination. Hypothesis-driven quantitative data are needed to justify the further use of this resource-intensive educational modality, specifically regarding whether using SPs to teach the neurological examination effects a long-term benefit on the application of neurological examination skills. Methods: This study is a cross-sectional analysis of prospectively collected data from medical students at Weill Cornell Medical College. The control group (n=129) received the standard curriculum. The intervention group (n=58) received the standard curriculum and an additional SP session focused on the neurologic examination during the second year of medical school. Student performance on the neurologic examination was assessed in the control and intervention groups via an OSCE administered during the fourth year of medical school. A Neurologic Physical Exam (NPE) score of 0.0 to 6.0 was calculated for each student based on a neurologic examination checklist completed by the SPs during the OSCE. Composite NPE scores in the control and intervention groups were compared with the unpaired t-test. Results: In the fourth year OSCE, composite NPE scores in the intervention group (3.5±1.1) were statistically significantly greater than those in the control group (2.2±1.1) (p<0.0001). Conclusions: SP sessions are an effective tool for teaching the neurologic examination. We determined that a single, structured SP session conducted as an adjunct to our traditional lectures and small groups is associated with a statistically significant improvement in student performance measured 2 years after the session

Attitudes of US medical trainees towards neurology education: "Neurophobia" - a global issue

<p>Abstract</p> <p>Background</p> <p>Several studies in the United Kingdom and Asia have suggested that medical students and residents have particular difficulty in diagnosing and managing patients with neurological problems. Little recent information is available for US trainees. We examined whether students and residents at a US university have difficulty in dealing with patients with neurological problems, identified the perceived sources of these difficulties and provide suggestions for the development of an effective educational experience in neurology.</p> <p>Methods</p> <p>A questionnaire was administered to third and fourth year medical students at a US school of medicine and to residents of an internal medicine residency program affiliated with that school. Perceived difficulties with eight medical specialties, including neurology, were examined. Methods considered to be most useful for learning medicine were documented. Reasons why neurology is perceived as difficult and ways to improve neurological teaching were assessed.</p> <p>Results</p> <p>152 surveys were completed. Participation rates varied, with medical students having higher response rates (> 50%) than medical residents (27%-48%). Respondents felt that neurology was the medical specialty they had least knowledge in (p < 0.001) and was most difficult (p < 0.001). Trainees also felt they had the least confidence when dealing with patients with neurological complaints (p < 0.001). Residents felt more competent in neurology than students (p < 0.001). The paramount reasons for perceived difficulties with neurology were the complexity of neuroanatomy, limited patient exposure and insufficient teaching. Transition from pre-clinical to clinical medicine led to a doubling of "poor" ratings for neurological teaching. Over 80% of the respondents felt that neurology teaching could be improved through greater exposure to patients and more bedside tutorials.</p> <p>Conclusions</p> <p>Medical students and residents at this US medical university found neurology difficult. Although this is consistent with prior reports from Europe and Asia, studies in other universities are needed to confirm generalizability of these findings. The optimal opportunity for improvement is during the transition from preclinical to clinical years. Enhanced integration of basic neurosciences and clinical neurology with emphasis on increased bedside tutorials and patient exposure should improve teaching. Studies are needed to quantify the effect of these interventions on confidence of trainees when dealing with patients presenting with neurological complaints.</p

Saliva levels of Abeta1-42 as potential biomarker of Alzheimer's disease: a pilot study

<p>Abstract</p> <p>Background</p> <p>Simple, non-invasive tests for early detection of degenerative dementia by use of biomarkers are urgently required. However, up to the present, no validated extracerebral diagnostic markers for the early diagnosis of Alzheimer disease (AD) are available. The clinical diagnosis of probable AD is made with around 90% accuracy using modern clinical, neuropsychological and imaging methods. A biochemical marker that would support the clinical diagnosis and distinguish AD from other causes of dementia would therefore be of great value as a screening test. A total of 126 samples were obtained from subjects with AD, and age-sex-matched controls. Additionally, 51 Parkinson's disease (PD) patients were used as an example of another neurodegenerative disorder. We analyzed saliva and plasma levels of β amyloid (Aβ) using a highly sensitive ELISA kit.</p> <p>Results</p> <p>We found a small but statistically significant increase in saliva Aβ₄₂levels in mild AD patients. In addition, there were not differences in saliva concentration of Aβ₄₂between patients with PD and healthy controls. Saliva Aβ₄₀expression was unchanged within all the studied sample. The association between saliva Aβ₄₂levels and AD was independent of established risk factors, including age or Apo E, but was dependent on sex and functional capacity.</p> <p>Conclusions</p> <p>We suggest that saliva Aβ₄₂levels could be considered a potential peripheral marker of AD and help discrimination from other types of neurodegenerative disorders. We propose a new and promising biomarker for early AD.</p

Haptic Perception of Object Curvature in Parkinson's Disease

The haptic perception of the curvature of an object is essential for adequate object manipulation and critical for our guidance of actions. This study investigated how the ability to perceive the curvature of an object is altered by Parkinson's disease (PD).Eight healthy subjects and 11 patients with mild to moderate PD had to judge, without vision, the curvature of a virtual "box" created by a robotic manipulandum. Their hands were either moved passively along a defined curved path or they actively explored the curved curvature of a virtual wall. The curvature was either concave or convex (bulging to the left or right) and was judged in two locations of the hand workspace--a left workspace location, where the curved hand path was associated with curved shoulder and elbow joint paths, and a right workspace location in which these joint paths were nearly linear. After exploring the curvature of the virtual object, subjects had to judge whether the curvature was concave or convex. Based on these data, thresholds for curvature sensitivity were established. The main findings of the study are: First, 9 out 11 PD patients (82%) showed elevated thresholds for detecting convex curvatures in at least one test condition. The respective median threshold for the PD group was increased by 343% when compared to the control group. Second, when distal hand paths became less associated with proximal joint paths (right workspace), haptic acuity was reduced substantially in both groups. Third, sensitivity to hand trajectory curvature was not improved during active exploration in either group.Our data demonstrate that PD is associated with a decreased acuity of the haptic sense, which may occur already at an early stage of the disease

The free β-subunit of human chorionic gonadotropin as a prognostic factor in renal cell carcinoma

The free β-subunit of human chorionic gonadotropin β is expressed in several nontrophoblastic tumours and this is usually associated with aggressive disease. Little is known about human chorionic gonadotropin β expression in renal cancer. We determined the pretreatment levels of human chorionic gonadotropin β in serum of patients with renal cell carcinoma, and studied whether elevated levels predicted the clinical outcome. Serum samples were collected before surgery from 177 patients with renal cell carcinoma and from 84 apparently healthy controls. Human chorionic gonadotropin β in serum was measured by a highly sensitive time-resolved immunofluorometric assay. The prognostic value of human chorionic gonadotropin β, and of usual clinical and pathological variables was analyzed by the Kaplan-Meier method, the log rank test and Cox multiple hazard regression. The serum concentrations of human chorionic gonadotropin β were increased in 23% of the renal cell carcinoma patients and they were significantly higher in patients with renal cell carcinoma than in controls (P<0.0001). The concentrations did not correlate with clinical stage and histopathological grade, but patients with increased human chorionic gonadotropin β levels had significantly shorter survival time than those with levels below the median (cut-off 1.2 pmol l−1, P=0.0029). In multivariate analysis human chorionic gonadotropin β, tumour stage and grade were independent prognostic variables. The serum concentration of human chorionic gonadotropin β is an independent prognostic variable in renal cell carcinoma. The preoperative value of human chorionic gonadotropin β in serum may be used to identify patents with increased risk of progressive disease

A controlled study of team-based learning for undergraduate clinical neurology education

<p>Abstract</p> <p>Background</p> <p>Team-based learning (TBL), a new active learning method, has not been reported for neurology education. We aimed to determine if TBL was more effective than passive learning (PL) in improving knowledge outcomes in two key neurology topics - neurological localization and neurological emergencies.</p> <p>Methods</p> <p>We conducted a modified crossover study during a nine-week internal medicine posting involving 49 third-year medical undergraduates, using TBL as the active intervention, compared against self-reading as a PL control, for teaching the two topics. Primary outcome was the mean percentage change in test scores immediately after (post-test 1) and 48 hours after TBL (post-test 2), compared to a baseline pre-test. Student engagement was the secondary outcome.</p> <p>Results</p> <p>Mean percentage change in scores was greater in the TBL versus the PL group in post-test 1 (8.8% vs 4.3%, p = 0.023) and post-test 2 (11.4% vs 3.4%, p = 0.001). After adjustment for gender and second year examination grades, mean percentage change in scores remained greater in the TBL versus the PL group for post-test 1 (10.3% vs 5.8%, mean difference 4.5%,95% CI 0.7 - 8.3%, p = 0.021) and post-test 2 (13.0% vs 4.9%, mean difference 8.1%,95% CI 3.7 - 12.5%, p = 0.001), indicating further score improvement 48 hours post-TBL. Academically weaker students, identified by poorer examination grades, showed a greater increase in scores with TBL versus strong students (p < 0.02). Measures of engagement were high in the TBL group, suggesting that continued improvements in scores 48 hours post-TBL may result from self-directed learning.</p> <p>Conclusions</p> <p>Compared to PL, TBL showed greater improvement in knowledge scores, with continued improvement up to 48 hours later. This effect is larger in academically weaker students. TBL is an effective method for improving knowledge in neurological localization and neurological emergencies in undergraduates.</p

Grasping isoluminant stimuli

We used a virtual reality setup to let participants grasp discs, which differed in luminance, chromaticity and size. Current theories on perception and action propose a division of labor in the brain into a color proficient perception pathway and a less color-capable action pathway. In this study, we addressed the question whether isoluminant stimuli, which provide only a chromatic but no luminance contrast for action planning, are harder to grasp than stimuli providing luminance contrast or both kinds of contrast. Although we found that grasps of isoluminant stimuli had a slightly steeper slope relating the maximum grip aperture to disc size, all other measures of grip quality were unaffected. Overall, our results do not support the view that isoluminance of stimulus and background impedes the planning of a grasping movement

Physical inactivity in Parkinson’s disease

Patients with Parkinson’s disease (PD) are likely to become physically inactive, because of their motor, mental, and emotional symptoms. However, specific studies on physical activity in PD are scarce, and results are conflicting. Here, we quantified daily physical activities in a large cohort of PD patients and another large cohort of matched controls. Moreover, we investigated the influence of disease-related factors on daily physical activities in PD patients. Daily physical activity data of PD patients (n = 699) were collected in the ParkinsonNet trial and of controls (n = 1,959) in the Longitudinal Aging Study Amsterdam (LASA); data were determined using the LAPAQ, a validated physical activity questionnaire. In addition, variables that may affect daily physical activities in PD were recorded, including motor symptoms, depression, disability in daily life, and comorbidity. Patients were physically less active; a reduction of 29% compared to controls (95% CI, 10–44%). Multivariate regression analyses demonstrated that greater disease severity, gait impairment, and greater disability in daily living were associated with less daily physical activity in PD (R2 = 24%). In this large study, we show that PD patients are about one-third less active compared to controls. While disease severity, gait, and disability in daily living predicted part of the inactivity, a portion of the variance remained unexplained, suggesting that additional determinants may also affect daily physical activities in PD. Because physical inactivity has many adverse consequences, work is needed to develop safe and enjoyable exercise programs for patients with PD