Clinical markers for identifying cholinergic deficits in Parkinson's disease

BackgroundCholinergic projection systems degeneration is associated with dopamine nonresponsive features of Parkinson's disease (PD). Cholinergic deficits are variable in nondemented PD. Identification of cholinergic deficits in PD may help with selection of suitable patients for targeted cholinergic drug treatment in PD. The objective of this retrospective multivariate predictor analysis study was to identify clinical markers indicative of cholinergic deficits in PD patients, as assessed by acetylcholinesterase ([11C]PMP) positron emission tomography.MethodsOne hundred thirty‐seven PD patients (34 female) participated; median modified Hoehn and Yahr score was 2.5 (range, 1‐4), average age 65.6 ± 7.4 years, and average duration of motor disease symptoms of 6.0 ± 4.2 years. Subjects were dichotomized as “normocholinergic” or “hypocholinergic” based on a 5th percentile cutoff from normal for the basal forebrain‐cortical and pedunculopontine nucleus‐thalamic cholinergic projection systems. Previously identified clinical indices of cholinergic denervation were used for statistical prediction of cholinergic deficits. Logistic regression determined which risk factors predicted cholinergic deficits. Sensitivity, specificity, and accuracy were determined for the (combinations of) significant predictor variables.ResultsForty‐nine (35.8%) hypocholinergic PD subjects were identified. The combination of rapid eye movement (REM) sleep behavior disorder (RBD) symptoms and fall history showed highest diagnostic accuracy (81.1%) for predicting combined thalamic and cortical cholinergic deficits. A combined assessment of 8.5 m walk time and lower score on the Montreal cognitive assessment scale provided diagnostic accuracy of 80.7% for predicting isolated cortical cholinergic denervation.ConclusionAssessment of clinical indices of cholinergic denervation may be useful for identifying suitable subjects for trials of targeted cholinergic drug treatments in PD. © 2014 International Parkinson and Movement Disorder SocietyPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110743/1/mds26061.pd

Impact of Supplemental Oxygen on Obstructive Sleep Apnea of Infants

Abstract: Treatment options may be limited for infants with obstructive sleep apnea when there is no surgically correctable upper airway lesion. We therefore evaluated, retrospectively, the efficacy of low-flow oxygen as a therapeutic option for infant obstructive sleep apnea. We reviewed the medical charts of 23 infants who had undergone a therapeutic trial of low-flow oxygen during polysomnography. Split-night polysomnography was used in 21/23 subjects while 2/23 had undergone two separate, full-night polysomnography sleep architecture and respiratory findings on the baseline polysomnogram segment that was obtained in room air were compared with the segment on low-flow oxygen (0.25–1 L/min). Wilcoxon signed rank or McNemar’s test were used as indicated for comparing apnea hypopnea index and measures of sleep architecture at baseline and with oxygen therapy. The mean (plus/minus SD) age of subjects was 4.8 (plus/minus 2.7) months, with 52% being males. The median apnea hypopnea index fell from a baseline of 18 (range 7–43) to 3 (range 1–19; p = 0.001) on oxygen. The baseline median obstructive/mixed apnea index decreased from 2 (range 1–16) to 1 during oxygen therapy (range 0–1; p = 0.003). Additionally, a significant decrease in central apnea index (median interquartile range (IQR) 1 (0–2) vs. 0 (0–1), p = 0.002) was noted. Sleep efficiency remained unaffected, while O2 saturation (SaO2) average and SaO2 nadir improved on oxygen. We were able to confirm the utility of low-flow oxygen in reducing central, obstructive, and mixed apneas and improving average oxygen saturation in infants with obstructive sleep apnea (OSA)

The 10‐year Landscape of United States‐Registered Parkinson Disease Clinical Trials: 2007–2016

BackgroundWe know little about how well the goals and results of clinical trials in Parkinson disease (PD) reflect the priorities of patients and the broader PD community.ObjectivesWe conducted a review of registered trials on clincialtrials.gov from 2007 to 2016 to explore whether PD trials have moved closer to the therapeutic priority goals articulated by the PD community.MethodsUsing the search terms: Parkinson, interventional trials, phase “0‐4,” we categorized therapeutic PD studies from clinicaltrials.gov between January 1, 2007 and December 31, 2016. Seven hundred and sixty‐six trials met the criteria for analysis. We explored temporal trends in the utilization of balance problems and falls; mood symptoms, including stress and anxiety; cognitive dysfunction, including dementia; and dyskinesias as primary outcomes. We analyzed trials where recruitment was listed as “completed” (n = 391) to explore publication rates.ResultsBalance problems and falls were listed as primary outcome measures in 125 studies (16.3%), cognitive measures in 48 (6.3%), mood features in 37 (4.8%), and dyskinesias in 30 (3.9%). Trials using balance problems and falls as a primary outcome increased in frequency per year between 2007 and 2016 (Z = ‐2.128, p = 0.033) unlike the proportion of trials evaluating cognitive dysfunction including dementia (Z = ‐0.380, p = 0.704), mood symptoms including stress and anxiety (Z = 0.345, p = 0.730), or dyskinesias (Z = 0.340, p = 0.734), which did not show temporal changes. 231 (59.1%) completed trials had results published in manuscript form as of 5/1/2017, leaving 40.9% of trials unpublished.ConclusionsPD trials focusing on balance problems and falls are becoming more common. About 40% of completed PD trials are unpublished, reflecting suboptimal utilization of participant efforts.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146271/1/mdc312665_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146271/2/mdc312665.pd

Educational attainment and motor burden in Parkinson's disease

ObjectiveGreater educational attainment is a protective factor for neurodegenerative dementias. If education earlier in life leads to greater cerebral reserve, it may play a similar protective role in Parkinson's disease (PD).MethodsWe conducted a cross‐sectional clinical imaging study of 142 subjects with PD. All subjects underwent [11C]dihydrotetrabenazine PET to confirm nigrostriatal dopaminergic denervation and brain MRI to estimate adjusted cortical gray matter volume (GMV).ResultsAfter adjusting for possible confounders, including cognitive and dopaminergic covariates, as well as nonspecific neurodegeneration covariates (age, disease duration, and total adjusted cortical GMV), lower years of education remained a significant predictor of higher total MDS‐UPDRS motor score (t = −3.28; P = 0.001). Education level associated inversely with white matter (WM) hyperintensities in a post‐hoc analysis (n = 83).ConclusionsHigher educational attainment is associated with lower severity of motor impairment in PD. This association may reflect an extranigral protective effect upon WM integrity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112215/1/mds26272.pd

Health and Economic Benefits of Improved Injury Prevention and Trauma Care Worldwide

Objectives: Injury is a significant source of morbidity and mortality worldwide, and often disproportionately affects younger, more productive members of society. While many have made the case for improved injury prevention and trauma care, health system development in low- and middle-income countries is often limited by resources. This study aims to determine the economic benefit of improved injury prevention and trauma care in low- and middle-income countries. Methods: This study uses existing data on injury mortality worldwide from the 2010 Global Burden of Disease Study to estimate the number of lives that could be saved if injury mortality rates in low- and middle-income countries could be reduced to rates in high-income countries. Using economic modeling – through the human capital approach and the value of a statistical life approach – the study then demonstrates the associated economic benefit of these lives saved. Results: 88 percent of injury-related deaths occur in low- and middle-income countries. If injury mortality rates in low- and middle-income countries were reduced to rates in high-income countries, 2,117,500 lives could be saved per year. This would result in between 49 million and 52 million disability adjusted life years averted per year, with discounting and age weighting. Using the human capital approach, the associated economic benefit of reducing mortality rates ranges from $245 to$261 billion with discounting and age weighting. Using the value of a statistical life approach, the benefit is between 758 and 786 billion dollars per year. Conclusions: Reducing injury mortality in low- and middle-income countries could save over 2 million lives per year and provide significant economic benefit globally. Further investments in trauma care and injury prevention are needed

Increased use of hypnotics in individuals with celiac disease: A nationwide case-control study

BACKGROUND: Although poor sleep is common in numerous gastrointestinal diseases, data are scarce on the risk of poor sleep in celiac disease. The objective of this study was to estimate the risk of repeated use of hypnotics among individuals with celiac disease as a proxy measure for poor sleep. METHODS: This is a nationwide case–control study including 2933 individuals with celiac disease and 14,571 matched controls from the general Swedish population. Poor sleep was defined as ≥2 prescriptions of hypnotics using prospective data from the National Prescribed Drug Register (data capture: July 2005-January 2008). We estimated odds ratios and hazard ratios for poor sleep before and after celiac disease diagnosis respectively. RESULTS: In this study, poor sleep was seen in 129/2933 individuals (4.4%) with celiac disease, as compared with 487/14,571 controls (3.3%) (odds ratio = 1.33; 95% CI = 1.08-1.62). Data restricted to sleep complaints starting ≥1 year before celiac disease diagnosis revealed largely unchanged risk estimates (odds ratio = 1.23; 95% CI = 0.88-1.71) as compared with the overall risk (odds ratio 1.33). The risk of poor sleep in celiac disease was essentially not influenced by adjustment for concomitant psychiatric comorbidity (n = 1744, adjusted odds ratio =1.26; 95% CI = 1.02-1.54) or restless legs syndrome (n = 108, adjusted odds ratio = 1.33; 95% CI = 1.08-1.63). Poor sleep was also more common after celiac disease diagnosis as compared with matched controls (hazard ratio = 1.36; 95% CI = 1.30-1.41). CONCLUSIONS: In conclusion, individuals with celiac disease suffer an increased risk of poor sleep, both before and after diagnosis. Although we cannot rule out that surveillance bias has contributed to our findings, our results are consistent with previous data suggesting that sleep complaints may be a manifestation of celiac disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12876-015-0236-z) contains supplementary material, which is available to authorized users

Pediatric restless legs syndrome diagnostic criteria: an update by the International Restless Legs Syndrome Study Group

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Color discrimination errors associate with axial motor impairments in Parkinson’s Disease

BackgroundVisual function deficits are more common in imbalance‐predominant compared to tremor‐predominant PD, suggesting a pathophysiological role of impaired visual functions in axial motor impairments.ObjectiveTo investigate the relationship between changes in color discrimination and motor impairments in PD while accounting for cognitive or other confounder factors.MethodsPD subjects (n = 49, age 66.7 ± 8.3 years; Hoehn & Yahr stage 2.6 ± 0.6) completed color discrimination assessment using the Farnsworth‐Munsell 100 Hue Color Vision Test, neuropsychological, motor assessments, and [11C]dihydrotetrabenazine vesicular monoamine transporter type 2 PET imaging. MDS‐UPDRS sub‐scores for cardinal motor features were computed. Timed Up & Go mobility and walking tests were assessed in 48 subjects.ResultsBivariate correlation coefficients between color discrimination and motor variables were significant only for the Timed Up & Go test (RS = 0.44, P = 0.0018) and the MDS‐UPDRS axial motor scores (RS = 0.38, P = 0.0068). Multiple regression confounder analysis using the Timed Up & Go as outcome parameter showed a significant total model (F(5,43) = 7.3, P < 0.0001) with significant regressor effects for color discrimination (standardized β = 0.32, t = 2.6, P = 0.012), global cognitive Z‐score (β = −0.33, t = −2.5, P = 0.018), duration of disease (β = 0.26, t = 1.8, P = 0.038), but not for age or striatal dopaminergic binding. The color discrimination test was also a significant independent regressor in the MDS‐UPDRS axial motor model (standardized β = 0.29, t = 2.4, P = 0.022; total model t(5,43) = 6.4, P = 0.0002).ConclusionsColor discrimination errors associate with axial motor features in PD independent of cognitive deficits, nigrostriatal dopaminergic denervation, and other confounder variables. These findings may reflect shared pathophysiology between color discrimination visual impairments and axial motor burden in PD.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141397/1/mdc312527.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141397/2/mdc312527_am.pd

Case Report Motor Speech Apraxia in a 70-Year-Old Man with Left Dorsolateral Frontal Arachnoid Cyst: A [ 18 F]FDG PET-CT Study

Motor speech apraxia is a speech disorder of impaired syllable sequencing which, when seen with advancing age, is suggestive of a neurodegenerative process affecting cortical structures in the left frontal lobe. Arachnoid cysts can be associated with neurologic symptoms due to compression of underlying brain structures though indications for surgical intervention are unclear. We present the case of a 70-year-old man who presented with a two-year history of speech changes along with decreased initiation and talkativeness, shorter utterances, and dysnomia. [ 18 F]Fluorodeoxyglucose (FDG) Positron Emission and Computed Tomography (PET-CT) and magnetic resonance imaging (MRI) showed very focal left frontal cortical hypometabolism immediately adjacent to an arachnoid cyst but no specific evidence of a neurodegenerative process