Citations

AbstractIntroductionRapid eye movement (REM) sleep behavior disorder (RBD) in Parkinson's disease (PD) is associated with differences in clinical phenotype, including dementia, autonomic loss, and gait dysfunction. The pathological basis for this remains unclear.MethodsParkinson's disease subjects in a longitudinal clinicopathologic study were screened for probable RBD with the Mayo Sleep Questionnaire. After death, semiquantitative analyses were conducted for synuclein, amyloid, neurofibrillary tangles, and cerebrovascular lesions.ResultsForty cases had probable RBD (PD+RBD), and 41 did not (PD‐RBD). Despite similar age at death (∼80 y) and disease duration (∼14.5 y), PD+RBD had increased synuclein deposition in all regions examined, with nine of 10 regions significantly different. The Lewy body 10‐region total score (scale = 0‐40) was 29.5 in PD+RBD versus 24.5 in PD‐RBD (Cohen‐d effect size = 0.79, P = 0.002). Cerebrovascular lesion burden was slightly higher in PD‐RBD.ConclusionsAlthough overlap occurs between groups, PD patients with probable RBD may have greater density and range of synuclein pathology on autopsy. © 2015 International Parkinson and Movement Disorder Society

Purpose Ocular vestibular evoked myogenic potentials (oVEMPs) are used to describe utricular/superior vestibular nerve function; however, optimal recording parameters have not been fully established. This study investigated the effect of repetition rate on air-conducted oVEMPs. Method Ten healthy adults were evaluated using 500-Hz tone bursts (4-ms duration, Blackman gating, 122 dB pSPL). Four repetition rates were used (1.6, 4.8, 8.3, and 26.6 Hz) and resulting oVEMP response presence, amplitude, amplitude asymmetry, and n1/p1 latency were assessed. Results Response presence was significantly reduced for 26.6 Hz using monaural stimulation and for 8.3 Hz and 26.6 Hz for binaural stimulation. For monaural stimulation using 1.6, 4.8, and 8.3 Hz, no significant differences were noted for amplitude or latency. Responses obtained using binaural stimulation demonstrated a significant effect of rate on amplitude, with 8.3 Hz producing significantly reduced amplitude. Binaural amplitudes were significantly larger than monaural contralateral responses but with reduced response presence. No significant differences were noted for latency or amplitude asymmetry. Conclusion Using repetition rates of approximately 5 Hz or less may produce more consistent oVEMP response presence with minimal effects on amplitude for monaural or binaural recordings.

Nonsteroidal antiinflammatory drugs (NSAIDs) are used in the management of a variety of conditions, but their prevalence is likely underreported as a result of widespread availability and the perception that nonprescription therapies are unnecessary to report during medication history taking. However, NSAIDs are associated with a number of adverse effects, especially in patients with cardiovascular disease (CVD). Patients with CVD and comorbidities for which NSAIDs may provide symptomatic relief (e.g., osteoarthritis, rheumatoid arthritis) tend to be older, which places them at greater risk of harm. For these reasons, the use of NSAIDs in patients with CVD is a significant public health concern. An understanding of the risks associated with NSAIDs is critical for clinicians across practice settings. In this review, we detail the safety of NSAIDs in patients with CVD, provide recommendations on their use in specific disease states, and discuss therapeutic alternatives.

Objectives: To report and compare patients’ experiences with acquired subglottic stenosis (AS) versus idiopathic subglottic and tracheal stenosis (ISTS). Methods: A survey was made available to patients with AS and ISTS. Results were analyzed for inter- and intragroup differences using a 2-tailed t test. Results: The study included 160 survey participants (AS n = 28; ISTS n = 132), with a predominance of female participants (82% AS, 98% ISTS). Acid reflux was the most prevalent comorbidity across groups (42%-43%). A significant difference in time to diagnosis was found between groups, with 32% of AS patients diagnosed within 3 months of symptom onset, compared to 2% with ISTS. A diagnosis delay greater than 18 months occurred for 58% of ISTS patients. There was no difference in treatment approach, with the most common treatment being balloon dilation, followed by laser dilation. Tracheal resection was performed in 36% of patients in both groups. Patient satisfaction with surgical outcomes was significantly higher after tracheal resection (76%) compared to other treatment modalities (39%). Conclusions: ISTS remains a diagnostic challenge as highlighted by the delay in diagnosis compared to AS. There appears to be no historical or symptomatic factors specific to ISTS. Additionally, patients report increased satisfaction and symptom resolution after tracheal resection.

The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain‐only donations and currently has banked more than 1600 brains. More than 430 whole‐body donations have been received since this service was commenced in 2005. The collective academic output of the BBDP is now described as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Most BBDP subjects are enrolled as cognitively normal volunteers residing in the retirement communities of metropolitan Phoenix, Arizona. Specific recruitment efforts are also directed at subjects with Alzheimer's disease, Parkinson's disease and cancer. The median age at death is 82. Subjects receive standardized general medical, neurological, neuropsychological and movement disorders assessments during life and more than 90% receive full pathological examinations by medically licensed pathologists after death. The Program has been funded through a combination of internal, federal and state of Arizona grants as well as user fees and pharmaceutical industry collaborations. Subsets of the Program are utilized by the US National Institute on Aging Arizona Alzheimer's Disease Core Center and the US National Institute of Neurological Disorders and Stroke National Brain and Tissue Resource for Parkinson's Disease and Related Disorders. Substantial funding has also been received from the Michael J. Fox Foundation for Parkinson's Research. The Program has made rapid autopsy a priority, with a 3.0‐hour median post‐mortem interval for the entire collection. The median RNA Integrity Number (RIN) for frozen brain and body tissue is 8.9 and 7.4, respectively. More than 2500 tissue requests have been served and currently about 200 are served annually. These requests have been made by more than 400 investigators located in 32 US states and 15 countries. Tissue from the BBDP has contributed to more than 350 publications and more than 200 grant‐funded projects.

Objective. To recognize intrathoracic abnormalities, including expansion or rupture of aortic aneurysms, as a source of acute onset vocal fold immobility.Methods. A case report and review of the literature.Results. An 85-year-old female with prior history of an aortic aneurysm presented to a tertiary care facility with sudden onset hoarseness. On laryngoscopy, the left vocal fold was immobile in the paramedian position. A CT scan obtained that day revealed a new, large hematoma surrounding the upper descending aortic stent graft consistent with an acute contained ruptured aortic aneurysm. She was referred to the emergency department for evaluation and treatment by vascular surgery. She was counseled regarding surgical options and ultimately decided not to pursue further treatment. Her vocal fold immobility was subsequently treated via office-based injection medialization two weeks after presentation and again 5 months after the initial injection which dramatically improved her voice. Follow-up CT scan at 8 months demonstrated a reduction of the hematoma. The left vocal cord remains immobile to date.Conclusion. Ortner’s syndrome, or cardiovocal syndrome, is hoarseness secondary to left recurrent laryngeal nerve palsy caused by cardiovascular pathology. It is a rare condition and, while typically presenting gradually, may also present with acute symptomatology.

Objectives To examine associations between specific inflammatory biomarkers and cognitive function in African Americans (AAs) and European Americans (EAs) with prevalent vascular risk factors. Design Cross‐sectional analysis using generalized estimating equations to account for familial clustering; standardized β‐coefficients, adjusted for age, sex, and education are reported. Setting Community cohort study in Jackson, Mississippi, and Rochester, Minnesota. Participants Genetic Epidemiology Network of Arteriopathy (GENOA)–Genetics of Microangiopathic Brain Injury (GMBI) Study participants. Measurements Associations between inflammation (high‐sensitivity C‐reactive protein (CRP), interleukin (IL)‐6, soluble tumor necrosis factor (TNF) receptor 1 and 2 (sTNFR1, sTNFR2)) and cognitive function (global, processing speed, language, memory, and executive function) were examined in AAs and EAs (N = 1,965; aged 26–95, 64% women, 52% AA, 75% with hypertension). Results In AAs, higher sTNFR2 was associated with poorer cognition in all domains (global: −0.11, P = .009; processing speed: −0.11, P < .001; language: −0.08, P = .002; memory: −0.09, P = .008; executive function: −0.07, P = .03); sTNFR1 was associated with slower processing speed (−0.08, P < .001) and poorer executive function (−0.08, P = .008); higher CRP was associated with slower processing speed (−0.04, P = .024), and higher IL6 was associated with poorer executive function (−0.07, P = .02). In EA, only higher sTNFR1 was associated with slower processing speed (−0.05, P = .007). Associations were not found between cognition and sTNFR2, CRP, or IL6 in EA. Conclusion In a population with high vascular risk, adverse associations between inflammation and cognitive function were especially apparent in AAs, primarily involving markers of TNFα activity.

Abstract The pathologic changes of Parkinson's disease ( PD ) and Progressive Supranuclear Palsy (PSP) have been reported to coexist, but whether PSP pathology modifies the clinical course of those individuals is unknown. The aim of this study was to determine whether clinical features of pathologically confirmed PD subjects with concomitant PSP pathology differ from those with PD alone. Subjects enrolled in the Arizona Study of Aging and Neurodegenerative Disorders had annual movement and cognitive evaluations from enrollment until death/autopsy. All cases between 1997 and 2014 with a final clinicopathological diagnosis of PD with or without PSP at autopsy were analyzed. Overall, 12 of the 125 cases with pathologically confirmed PD had coexisting PSP pathology (9.6%). Those with PD ‐ PSP had more‐prominent postural instability, body bradykinesia, difficulty arising from a chair, and falls; asymmetric onset was less common in this group. Downgaze palsy and square wave jerks were infrequent in both groups. Gender, age at death, disease duration, rate of dementia, and presence of rest tremor did not differ between groups. Only 58% of subjects in the PD ‐ PSP group were correctly given a final diagnosis in life of PD, compared to 91% of those with PD alone. The combination of PD and PSP pathology yields a heterogeneous clinical syndrome that often resembles PD, but may be more symmetric at onset and have more‐prominent postural instability and falls. Our observations suggest that coexisting PSP pathology may be an important factor contributing to the clinical heterogeneity in PD and a potential confounder in diagnosis.

A proof of principle pharmacogenomic translational study was used as a case example to explore Biobank Community Advisory Board (CAB) member views about placing genomic information into the medical record and to establish how CAB input could affect research design. CAB members expressed enthusiasm for the potential benefit of the research discussed, yet voiced concerns regarding the recruitment and consent materials. They discussed the value of genomic research and its clinical utility; the risk of genetic discrimination; and personal ownership of genomic data. Members distinguished between indirect benefits to future generations and individual risk to research participants. Feedback was used to revise the recruitment and consent materials. Results highlight tensions reported between the public’s support for genomic research and concerns with genomic information in the medical record and its use in medical decision-making.