Factors Associated With Ambulatory Activity in De Novo Parkinson Disease.

BACKGROUND AND PURPOSE: Objective ambulatory activity during daily living has not been characterized for people with Parkinson disease prior to initiation of dopaminergic medication. Our goal was to characterize ambulatory activity based on average daily step count and examine determinants of step count in nonexercising people with de novo Parkinson disease. METHODS: We analyzed baseline data from a randomized controlled trial, which excluded people performing regular endurance exercise. Of 128 eligible participants (mean ± SD = 64.3 ± 8.6 years), 113 had complete accelerometer data, which were used to determine daily step count. Multiple linear regression was used to identify factors associated with average daily step count over 10 days. Candidate explanatory variable categories were (1) demographics/anthropometrics, (2) Parkinson disease characteristics, (3) motor symptom severity, (4) nonmotor and behavioral characteristics, (5) comorbidities, and (6) cardiorespiratory fitness. RESULTS: Average daily step count was 5362 ± 2890 steps per day. Five factors explained 24% of daily step count variability, with higher step count associated with higher cardiorespiratory fitness (10%), no fear/worry of falling (5%), lower motor severity examination score (4%), more recent time since Parkinson disease diagnosis (3%), and the presence of a cardiovascular condition (2%). DISCUSSION AND CONCLUSIONS: Daily step count in nonexercising people recruited for this intervention trial with de novo Parkinson disease approached sedentary lifestyle levels. Further study is warranted for elucidating factors explaining ambulatory activity, particularly cardiorespiratory fitness, and fear/worry of falling. Clinicians should consider the costs and benefits of exercise and activity behavior interventions immediately after diagnosis of Parkinson disease to attenuate the health consequences of low daily step count.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A170).

Validation of secondary data sources to identify Parkinson disease against clinical diagnostic criteria.

Parkinson disease (PD) is the second most common neurodegenerative disorder. Its diagnosis relies solely on a clinical examination and is not straightforward because no diagnostic test exists. Large, population-based, prospective cohort studies designed to examine other outcomes that are more common than PD might provide cost-efficient alternatives for studying the disease. However, most cohort studies have not implemented rigorous systematic screening for PD. A majority of epidemiologic studies that utilize population-based prospective designs rely on secondary data sources to identify PD cases. Direct validation of these secondary sources against clinical diagnostic criteria is lacking. The Framingham Heart Study has prospectively screened and evaluated participants for PD based on clinical diagnostic criteria. We assessed the predictive value of secondary sources for PD identification relative to clinical diagnostic criteria in the Framingham Heart Study (2001-2012). We found positive predictive values of 1.0 (95% confidence interval: 0.868, 1.0), 1.0 (95% confidence interval: 0.839, 1.0), and 0.50 (95% confidence interval: 0.307, 0.694) for PD identified from self-report, use of antiparkinsonian medications, and Medicare claims, respectively. The negative predictive values were all higher than 0.99. Our results highlight the limitations of using only Medicare claims data and suggest that population-based cohorts may be utilized for the study of PD determined via self-report or medication inventories while preserving a high degree of confidence in the validity of PD case identification.

Patterns of Motor and Non-Motor Features in Medication-Naïve Parkinsonism.

BACKGROUND: Parkinsonism is defined by motor features (tremor, bradykinesia, rigidity, and postural instability). Accompanying non-motor features (e.g. cognitive, autonomic, sleep disturbances) are underrecognized and undertreated. We hypothesized that clinical patterns occurring in early, medication-naïve Parkinsonism are distinguished by features such as tremor, sleep, autonomic, and cognitive dysfunction. METHODS: Clinical and neuroimaging data were obtained in the Parkinson's Progression Marker Initiative. Group comparisons of Parkinsonism with dopaminergic deficits (PDD) (n = 388), controls (n = 196), and Parkinsonism with scans without evidence of dopaminergic deficits (n = 64) were done with ANOVA, chi-square, and post-hoc pairwise tests. To examine clinical patterns within the PDD group, k-means clustering was performed with non-motor or motor features, or both. RESULTS: Among PDD, 4 non-motor patterns (% of PDD) (impulsive (14.9%), sleep-autonomic (22.9%), cognitive-olfactory (18.0%), and mild (44.1%)), 4 motor patterns (tremor plus bradykinesia (56.2%), tremor without bradykinesia (16.2%), postural instability (6.7%) and no tremor (20.9%)) and 5 combined motor/non-motor patterns (tremor with bradykinesia (42.3%), tremor without bradykinesia (15.5%), no tremor and mild non-motor features (17.0%), postural instability with sleep-autonomic disturbances (6.7%) and oldest onset cognitive-olfactory (18.6%)) were observed. CONCLUSIONS: To our knowledge, this is the first description of non-motor clinical patterns in early, medication-naïve Parkinsonism, suggesting that such features are intrinsic to Parkinsonian disorders.

Enhancing case ascertainment of Parkinson's disease using Medicare claims data in a population-based cohort: the Cardiovascular Health Study.

PURPOSE: We sought to improve a previous algorithm to ascertain Parkinson's disease (PD) in the Cardiovascular Health Study by incorporating additional data from Medicare outpatient claims. We compared our results to the previous algorithm in terms of baseline prevalence and incidence of PD, as well as associations with baseline smoking characteristics. METHODS: Our original case ascertainment used self-reported diagnosis, antiparkinsonian medication, and hospitalization discharge International Classification of Diseases-Ninth version code. In this study, we incorporated additional data from fee-for-service Medicare claims, extended follow-up time, review of hospitalization records, and adjudicated cause of death. Two movement disorders specialists adjudicated final PD status. We used logistic regression models and controlled for age, sex, African American race, and education. RESULTS: We identified 75 additional cases but reclassified 80 previously identified cases as not having PD. We observed significant inverse association with smoking status (odds ratio = 0.42; 95% confidence interval (CI) = 0.22, 0.79), and inverse linear trends with pack-years (p = 0.005), and cigarettes per day (p = 0.019) with incident PD. All estimates were stronger than those from the previous algorithm. CONCLUSIONS: Our enhanced method did not alter prevalence and incidence estimates compared with our previous algorithm. However, our enhanced method provided stronger estimates of association, potentially due to reduced level of disease misclassification.

A penal problem: the increasing incidence of implantation of penile foreign bodies.

Our objective is to describe a novel presentation of subcutaneous penile insertion of foreign bodies. This is a practice performed globally and mostly has been reported outside of the United States. We present three cases of incarcerated males that implanted sculpted dominos into the penile subcutaneous tissue. The patients presented with erosion of the foreign bodies through the skin without evidence of infection. We believe that insertion of foreign bodies into penile subcutaneous tissue by incarcerated American males for sexual enhancement is more widespread than previously reported. Erosion is a novel presentation.

Incidence of renal artery pseudoaneurysm following open and minimally invasive partial nephrectomy: a systematic review and comparative analysis.

PURPOSE: Partial nephrectomy is performed for renal masses as a means of preserving renal function. Renal artery pseudoaneurysm is a potential complication of partial nephrectomy. We determined the incidence of renal artery pseudoaneurysm after open and minimally invasive partial nephrectomy, and performed a comparative analysis. MATERIALS AND METHODS: We queried the Ovid Medline® and PubMed® databases to locate published reports of renal artery pseudoaneurysm after partial nephrectomy. Studies were included in comparative analysis if they were in English and showed the total number of procedures performed and perioperative complications. RESULTS: Included studies represented a total of 5,229 patients, of whom 2,494 and 2,735 underwent open and minimally invasive partial nephrectomy, respectively. A total of 25 and 52 renal artery pseudoaneurysms were reported after open and minimally invasive procedures (weighted 1.00% and 1.96%, respectively). The difference between these 2 values was statistically significant (p ≤ 0.001). Patients diagnosed with renal artery pseudoaneurysm presented a mean of 14.9 days after surgery and 87.3% of them had gross hematuria at presentation. Almost all patients with renal artery pseudoaneurysm were treated with percutaneous angioembolization with 96% success. CONCLUSIONS: Although it is rare, the risk of renal artery pseudoaneurysm after partial nephrectomy is significant and should be high on the differential for a patient who presents postoperatively with gross hematuria. The incidence of renal artery pseudoaneurysm is higher after minimally invasive partial nephrectomy than after an open approach. Angioembolization for renal artery pseudoaneurysm after partial nephrectomy offers an excellent success rate and minimal patient morbidity.

Cardiovascular dysautonomia in Parkinson disease: from pathophysiology to pathogenesis.

Signs or symptoms of impaired autonomic regulation of circulation often attend Parkinson disease (PD). This review covers biomarkers and mechanisms of autonomic cardiovascular abnormalities in PD and related alpha-synucleinopathies. The clearest clinical laboratory correlate of dysautonomia in PD is loss of myocardial noradrenergic innervation, detected by cardiac sympathetic neuroimaging. About 30-40% of PD patients have orthostatic hypotension (OH), defined as a persistent, consistent fall in systolic blood pressure of at least 20 mmHg or diastolic blood pressure of at least 10 mmHg within 3 min of change in position from supine to standing. Neuroimaging evidence of cardiac sympathetic denervation is universal in PD with OH (PD+OH). In PD without OH about half the patients have diffuse left ventricular myocardial sympathetic denervation, a substantial minority have partial denervation confined to the inferolateral or apical walls, and a small number have normal innervation. Among patients with partial denervation the neuronal loss invariably progresses over time, and in those with normal innervation at least some loss eventually becomes evident. Thus, cardiac sympathetic denervation in PD occurs independently of the movement disorder. PD+OH also entails extra-cardiac noradrenergic denervation, but this is not as severe as in pure autonomic failure. PD+OH patients have failure of both the parasympathetic and sympathetic components of the arterial baroreflex. OH in PD therefore seems to reflect a "triple whammy" of cardiac and extra-cardiac noradrenergic denervation and baroreflex failure. In contrast, most patients with multiple system atrophy, which can resemble PD+OH clinically, do not have evidence for cardiac or extra-cardiac noradrenergic denervation. Catecholamines in the neuronal cytoplasm are potentially toxic, via spontaneous and enzyme-catalyzed oxidation. Normally cytoplasmic catecholamines are efficiently taken up into vesicles via the vesicular monoamine transporter. The recent finding of decreased vesicular uptake in Lewy body diseases therefore suggests a pathogenetic mechanism for loss of catecholaminergic neurons in the periphery and brain. Parkinson disease (PD) is one of the most common chronic neurodegenerative diseases of the elderly, and it is likely that as populations age PD will become even more prevalent and more of a public health burden. Severe depletion of dopaminergic neurons of the nigrostriatal system characterizes and likely produces the movement disorder (rest tremor, slowness of movement, rigid muscle tone, and postural instability) in PD. Over the past two decades, compelling evidence has accrued that PD also involves loss of noradrenergic neurons in the heart. This finding supports the view that loss of catecholaminergic neurons, both in the nigrostriatal system and the heart, is fundamental in PD. By the time PD manifests clinically, most of the nigrostriatal dopaminergic neurons are already lost. Identifying laboratory measures-biomarkers-of the disease process is therefore crucial for advances in treatment and prevention. Deposition of the protein, alpha-synuclein, in the form of Lewy bodies in catecholaminergic neurons is a pathologic hallmark of PD. Alpha-synucleinopathy in autonomic neurons may occur early in the pathogenetic process. The timing of cardiac noradrenergic denervation in PD is therefore a key issue. This review updates the field of autonomic cardiovascular abnormalities in PD and related disorders, with emphasis on relationships among striatal dopamine depletion, sympathetic noradrenergic denervation, and alpha-synucleinopathy.

Cardiovascular physiology in premotor Parkinson's disease: a neuroepidemiologic study.

Changes in cardiovascular physiology in Parkinson's disease (PD) are common and may occur prior to diagnostic parkinsonian motor signs. We investigated associations of electrocardiographic (ECG) abnormalities, orthostasis, heart rate variability, and carotid stenosis with the risk of PD diagnosis in the Cardiovascular Health Study, a community-based cohort of older adults. ECG abnormality, orthostasis (symptomatic or asymptomatic), heart rate variability (24-hour Holter monitoring), and any carotid stenosis (≥1%) by ultrasound were modeled as primary predictors of incident PD diagnosis using multivariable logistic regression. Incident PD cases were identified by at least 1 of the following: self-report, antiparkinsonian medication use, and ICD-9. If unadjusted models were significant, they were adjusted or stratified by age, sex, and smoking status, and those in which predictors were still significant (P ≤ .05) were also adjusted for race, diabetes, total cholesterol, low-density lipoprotein, blood pressure, body mass index, physical activity, education level, stroke, and C-reactive protein. Of 5888 participants, 154 incident PD cases were identified over 14 years of follow-up. After adjusting models with all covariates, those with any ECG abnormality (odds ratio [OR], 1.45; 95% CI, 1.02-2.07; P = .04) or any carotid stenosis (OR, 2.40; 95% CI, 1.40-4.09; P = .001) at baseline had a higher risk of incident PD diagnosis. Orthostasis and heart rate variability were not significant predictors. This exploratory study suggests that carotid stenosis and ECG abnormalities occur prior to motor signs in PD, thus serving as potential premotor features or risk factors for PD diagnosis. Replication is needed in a population with more thorough ascertainment of PD onset.

Partial nephrectomy in two patients with known T3a tumours involving the renal vein.

UNLABELLED: Study Type--Therapy (case series). Level of Evidence 4. What's known on the subject? And what does the study add? Although nephron-sparing surgery (NSS) has became accepted therapy for T1 tumours, radical nephrectony is considered the best therapy for T3a tumours involving the renal vein. NSS can be considered in T3a or greater tumours if imperative indications exist, such as bilateral disease or solitary kidney. However, there is little published data on the characteristics of these patients, the impact of surgery on their renal function, and long-term oncologic outcomes. This study profiles single-institution experience with nephron-sparing surgery for known T3a tumours involving the renal vein, including patient characteristics, tumour characteristics, preoperative and follow-up imaging, preoperative and follow-up estimated glomerular filtration rate, length of temporary postoperative haemodialysis, and oncologic outcome. Additionally, we compare this to other published data on nephron-sparing surgery for similar tumors. OBJECTIVE: • To present two patients with T3a tumours involving the renal vein who underwent nephron-sparing surgery (NSS) for imperative reasons. PATIENTS AND METHODS: • Retrospective chart review of patients who underwent NSS for renal cell carcinoma (RCC) with known renal vein tumour thrombus (RVTT). • Both patients underwent open partial nephrectomy and renal vein thrombectomy of a solitary kidney. • Primary outcomes of the study include radiographic evidence of recurrence, haemodialysis requirement and estimated glomerular filtration rate (eGFR) before and after surgery. RESULTS: • Patient 1 is 24 months from NSS and has no evidence of recurrence based on CT scan. His final pathology revealed a 9-cm, T3a, clear cell, Fuhrman grade II carcinoma. He spent 42 days on haemodialysis and is now off all dialysis. His preoperative and most recent eGFR are 48 and 23 mL/min/1.73 m(2) based on the Modification of Diet in Renal Disease (MDRD) equation and 69.4 and 29.8 mL/min by the Cockcroft-Gault equation. • Patient 2 is 9 months from NSS and has no evidence of recurrence based on CT scan. Her final pathology revealed a 6-cm, T3a, clear cell, Fuhrman grade II-III carcinoma. She spent 30 days on haemodialysis and is now off all dialysis. Her preoperative and most recent eGFR are 58 and 30 mL/min/1.73 m(2) based on the MDRD equation and 62.2 and 32.8 mL/min by the Cockcroft-Gault equation. CONCLUSION: • Based on our review, preservation of renal function and favourable oncological outcome can be accomplished with NSS in patients with known stage T3a RCC with RVTT and should be considered in carefully selected patients.

Olfactory dysfunction and parasympathetic dysautonomia in Parkinson's disease.

OBJECTIVE: Olfactory impairment occurs early in Parkinson's disease (PD), as may dysautonomia. We investigated the relationship between olfaction and dysautonomia as well as other non-motor manifestations of PD. METHODS: Olfaction [University of Pennsylvania Smell Identification Test (UPSIT)], autonomic function in the pupillary (constriction and redilation velocity) and cardiac systems (resting low- and high-frequency heart rate variability (LF and HF HRV), positional changes in systolic blood pressure), neuropsychiatric function [Mini-mental Status Exam (MMSE)], Hamilton Depression Scale, activities of daily living [(ADLs), Schwab and England ADLs scale], quality of life [Short Form-36 health survey, PD Questionnaire 39 (PDQ-39)], and other non-motor symptoms [Non-motor Symptoms Scale (NMSS)] were simultaneously assessed in 33 participants (15 PD, 18 controls). Group comparisons, Spearman's coefficients and non-parametric rank-based regression were employed to characterize relationships between olfaction and non-motor features. RESULTS: Smell scores were lower in the PD group and correlated positively with pupil constriction velocity and HF HRV. Smell scores were correlated negatively with PDQ-39 and gastrointestinal items of the NMSS and positively with MMSE and Schwab and England ADLs. These correlated measures were not significant terms in regression models of smell scores in which age and PD diagnosis were significant and accounted for over half of the variability (R-squared 0.52­0.58). INTERPRETATION: This study suggests olfactory involvement occurs with parasympathetic dysautonomia in the pupillary and cardiovascular systems, involving both age-related and PD-related processes. Other non-motor features are concurrently involved, supporting the notion that aging and PD have widespread effects involving discrete portions of the autonomic and olfactory systems.

Pupillary unrest correlates with arousal symptoms and motor signs in Parkinson disease.

BACKGROUND: Arousal symptoms (e.g., sleepiness) are common in Parkinson's disease, and pupillary unrest (spontaneous changes in pupil diameter) is positively associated with sleepiness. We explored pupillary unrest in Parkinson's disease. METHODS: Arousal symptoms (Epworth sleepiness scale and sleep/fatigue domain of the nonmotor symptoms scale for Parkinson's disease) and pupillary unrest were assessed in 31 participants (14 patients with Parkinson's disease, 17 controls). Effect sizes and t tests compared patients with Parkinson's disease with control participants. Correlation coefficients were calculated among arousal symptoms, pupillary unrest, and Unified Parkinson Disease Rating Scale Part III. Linear regression was performed with arousal symptoms or pupillary unrest as outcome. RESULTS: Participants with Parkinson's disease reported more arousal symptoms than controls. Pupillary unrest, arousal symptoms, and Unified Parkinson Disease Rating Scale Part III were positively correlated. The association between nonmotor symptoms scale-sleep score and pupillary unrest was higher in participants with Parkinson's disease than controls and higher in those with more Parkinsonian motor signs. Unified Parkinson Disease Rating Scale Part III was positively associated with pupillary unrest. CONCLUSIONS: Pupillary unrest correlates with motor and nonmotor features associated with Lewy-related pathology, suggesting it may be a nonmotor marker of progression in Parkinson's disease. © 2011 Movement Disorder Society.

Clinical Presentation and Prognosis of Common Movement Disorders.

Great progress has been made in expanding our understanding of the natural history of movement disorders, leading to impressive advancements in their medical and surgical management. Movement disorders are a diverse group of diseases, varying widely in clinical characteristics and evolution. Some are monosymptomatic while others have associated motor and nonmotor features. Some are static while others follow a progressive course. This chapter will review common primary and secondary movement disorders: Parkinson disease and other forms of Parkinsonism, essential tremor and its differential diagnoses, dystonia and tic disorders. Herein, we will provide an overview of the clinical presentation and prognosis of the primary and secondary movement disorders most relevant to discussions of surgical candidacy.

Ciprofloxacin-Resistant Bacteria on Pre-Prostate Biopsy Rectal Swab Culture: A Northwest Ohio Study.

BACKGROUND: Ciprofloxacin is given to patients routinely prior to trans-rectal prostate biopsy. However bacterial resistance to this antibiotic has increased nationally resulting in increased infectious complications after prostate biopsy. In our study we aimed to quantify the percentage of older northwestern Ohio males harboring ciprofloxacin-resistant bacteria in the rectal vault and to assess if resistance is increasing over time. METHODS: After Institutional Review Board approval, a retrospective chart review of all patients who underwent rectal swab culture within the Department of Urology at The University of Toledo Medical Center between January 1, 2012 and December 31, 2015 was completed. Patient demographic data were collected including the presence of ciprofloxacin resistance bacteria. To test for significant differences, χ2 and analysis of variance (ANOVA) analyses were completed where applicable. RESULTS: During the study period 311 swabs for resistant organisms were completed. The average age at time of swab was 64 (± 8.7 standard deviation [SD]) years old. Resistance rates were 13.2%, 13.8%, 19.5%, and 13.3% in 2012, 2013, 2014, and 2015, respectively. We found no statistically significant difference in resistances across years. Additionally, previous biopsy and age were not associated with ciprofloxacin resistance. CONCLUSIONS: Resistance to ciprofloxacin in the rectal vaults of older northwestern Ohio males is significant but appears to be stable over the study period. Previous biopsy and increased age do not appear to be risk factors for fluoroquinolone resistance. Given the relatively high rate of resistance in our population we recommend rectal swabs prior to prostate biopsy to assist in antibiotic agent choice.

Effect of High-Intensity Treadmill Exercise on Motor Symptoms in Patients With De Novo Parkinson Disease: A Phase 2 Randomized Clinical Trial.

Importance: Parkinson disease is a progressive neurologic disorder. Limited evidence suggests endurance exercise modifies disease severity, particularly high-intensity exercise. Objectives: To examine the feasibility and safety of high-intensity treadmill exercise in patients with de novo Parkinson disease who are not taking medication and whether the effect on motor symptoms warrants a phase 3 trial. Design, Setting, and Participants: The Study in Parkinson Disease of Exercise (SPARX) was a phase 2, multicenter randomized clinical trial with 3 groups and masked assessors. Individuals from outpatient and community-based clinics were enrolled from May 1, 2012, through November 30, 2015, with the primary end point at 6 months. Individuals with idiopathic Parkinson disease (Hoehn and Yahr stages 1 or 2) aged 40 to 80 years within 5 years of diagnosis who were not exercising at moderate intensity greater than 3 times per week and not expected to need dopaminergic medication within 6 months participated in this study. A total of 384 volunteers were screened by telephone; 128 were randomly assigned to 1 of 3 groups (high-intensity exercise, moderate-intensity exercise, or control). Interventions: High-intensity treadmill exercise (4 days per week, 80%-85% maximum heart rate [n = 43]), moderate-intensity treadmill exercise (4 days per week, 60%-65% maximum heart rate [n = 45]), or wait-list control (n = 40) for 6 months. Main Outcomes and Measures: Feasibility measures were adherence to prescribed heart rate and exercise frequency of 3 days per week and safety. The clinical outcome was 6-month change in Unified Parkinson's Disease Rating Scale motor score. Results: A total of 128 patients were included in the study (mean [SD] age, 64 [9] years; age range, 40-80 years; 73 [57.0%] male; and 108 [84.4%] non-Hispanic white). Exercise rates were 2.8 (95% CI, 2.4-3.2) days per week at 80.2% (95% CI, 78.8%-81.7%) maximum heart rate in the high-intensity group and 3.2 (95% CI, 2.8-3.6; P = .13) days per week at 65.9% (95% CI, 64.2%-67.7%) maximum heart rate in the moderate-intensity group (P < .001). The mean change in Unified Parkinson's Disease Rating Scale motor score in the high-intensity group was 0.3 (95% CI, -1.7 to 2.3) compared with 3.2 (95% CI, 1.4 to 5.1) in the usual care group (P = .03). The high-intensity group, but not the moderate-intensity group, reached the predefined nonfutility threshold compared with the control group. Anticipated adverse musculoskeletal events were not severe. Conclusions and Relevance: High-intensity treadmill exercise may be feasible and prescribed safely for patients with Parkinson disease. An efficacy trial is warranted to determine whether high-intensity treadmill exercise produces meaningful clinical benefits in de novo Parkinson disease. Trial Registration: clinicaltrials.gov Identifier: NCT01506479.