Citations

Dementia is a frequent complication of Parkinson's disease (PD). About half of PD dementia (PDD) is hypothesized to be due to progression of the underlying Lewy body pathology into limbic regions and the cerebral cortex while the other half is thought to be due to coexistent Alzheimer's disease (AD). Clinically, however, these are indistinguishable. The spread of amyloid plaques to the striatum has been reported to be a sensitive and specific indicator of dementia due to AD. The purpose of the present study was to determine if the presence of striatal plaques might also be a useful indicator of the presence of diagnostic levels of AD pathology within PD subjects. We analyzed neuropathologically-confirmed cases of PD without dementia (PDND, N = 31), PDD without AD (PDD, N = 31) and PD with dementia meeting clinicopathological criteria for AD (PDAD, N = 40). The minimum diagnostic criterion for AD was defined as including a clinical history of dementia, moderate or frequent CERAD cortical neuritic plaque density and Braak neurofibrillary stage III-VI. Striatal amyloid plaque densities were determined using Campbell-Switzer and Thioflavine S stains. Striatal plaque densities were significantly higher in PDAD compared to PDD (p < 0.001). The presence of striatal plaques was approximately 80% sensitive and 80% specific for predicting AD. In comparison, the presence of cerebral cortex plaques alone was highly sensitive (100%) but had poor specificity (48% to 55%). The results suggest that striatal amyloid imaging may be clinically useful for making the distinction between PDD and PDAD.

Aims Novel therapies are needed for recurrent pericarditis, particularly when corticosteroid dependent and colchicine resistant. Based on limited data, interleukin-1 blockade with anakinra may be beneficial. The aim of this multicentre registry was to evaluate the broader effectiveness and safety of anakinra in a ‘real world’ population. Methods and results This registry enrolled consecutive patients with recurrent pericarditis who were corticosteroid dependent and colchicine resistant and treated with anakinra. The primary outcome was the pericarditis recurrence rate after treatment. Secondary outcomes included emergency department visits, hospitalisations, corticosteroid use and adverse events. Among 224 patients (46 ± 14 years old, 63% women, 75% idiopathic), the median duration of disease was 17 months (interquartile range 9–33). Most patients had elevated C-reactive protein (91%) and pericardial effusion (88%). After a median treatment of 6 months (3–12), pericarditis recurrences were reduced six-fold (2.33–0.39 per patient per year), emergency department admissions were reduced 11-fold (1.08–0.10 per patient per year), hospitalisations were reduced seven-fold (0.99–0.13 per patient per year). Corticosteroid use was decreased by anakinra (respectively from 80% to 27%; P < 0.001). No serious adverse events occurred; adverse events consisted mostly of transient skin reactions (38%) at the injection site. Adverse events led to discontinuation in 3%. A full-dose treatment duration of over 3 months followed by a tapering period of over 3 months were the therapeutic schemes associated with a lower risk of recurrence. Conclusion In patients with recurrent pericarditis, anakinra appears efficacious and safe in reducing recurrences, emergency department admissions and hospitalisations.

INTRODUCTION: Options to treat medically refractory gastroparesis are limited. Gastric peroral endoscopic myotomy (G-POEM) is a novel minimally invasive technique in endosurgery that has shown promising results. Data is limited as to its efficacy, safety, predictive factors and its comparability to surgical pyloroplasty. The aim of our study was to synthesize and analyze the clinical outcomes of GPOEM by meta-analysis methods. METHODS: We searched multiple databases from inception through March 2019 to identify studies that reported on G-POEM and surgical pyloroplasty in gastroparesis. Our primary outcome was to analyze the pooled rates of gastroparesis cardinal symptom index (GCSI) score and 4-hr gastric emptying study (GES) results, with G-POEM. Similar outcomes with surgical pyloroplasty was used as a comparator group. RESULTS: 332 and 375 patients underwent G-POEM (11studies) and pyloroplasty (7studies), respectively. The pooled rate of clinical success, based on the GCSI score, with G-POEM was 75.8% (95% CI 68.1-82.1, I 2 = 50) and with pyloroplasty was 77.3% (95% CI 66.4-85.4, I 2 = 0), with no significance, P = 0.81. The pooled rate of clinical success, based on the 4-hour GES results, with GPOEM was 85.1% (95% CI 68.9-93.7, I 2 = 74) and with pyloroplasty was 84% (95% CI 64.4-93.8, I 2 = 81), with no significance, P = 0.91. The pooled rate of mean pre-G-POEM GCSI score was 3.4 (95% CI 3.1-3.7, I 2 = 89) and post-G-POEM GCSI score was 1.8 (95% CI 1.4-2.1, I 2 = 89), with statistical significance ( P = 0.001). The pooled pre-G-POEM 4-hr GES was 49.9% (95% CI 41.6-58.3, I 2 = 94) and post-G-POEM 4-hr GES was 20.6% (95% CI 12.3-28.8, I 2 = 77), with statistical significance ( P = 0.001). The pre and post pyloroplasty 4-hr GES results were 36% (95% CI 32.7-39.3, I 2 = 88) and 3.9% (95% CI 2.3-5.5, I 2 = 43), respectively ( P = 0.001). The pre and post pyloroplasty GCSI score was not analyzed due to paucity in data. The overall adverse events were comparable (11%, 5.9-19.8, I 2 = 66 vs 11.4%, 5-24, I 2 = 69, P = 0.95). Based on meta-regression analysis, idiopathic-gastroparesis, prior treatment with botulinum toxin and gastric-stimulator seemed to predict clinical success with G-POEM. CONCLUSION: G-POEM demonstrates clinical success in treating refractory gastroparesis with comparable outcomes to pyloroplasty. Idiopathic gastroparesis, prior treatment with botulinum injection and gastric stimulator appear to have positive predictive effects on the 4-hr GES results after G-POEM.

ABSTRACT Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk of future fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring for adverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). © 2019 American Society for Bone and Mineral Research.

Abstract This study was designed to correlate clinical findings with the extent of pathologic a-synuclein (aSyn) in the brain using the Unified Staging System for Lewy Body disorders (USSLB). Data from 280 cases from the Arizona Study of Aging and Neurodegenerative Disorders are presented. Each case had a complete USSLB staging and at least 1 full research clinical assessment, including subspecialty neurologist-administered movement and cognitive evaluation. Of the 280, 25.7% were cognitively normal, 8.6% had mild cognitive impairment, and 65.7% had dementia. All cases could be categorized into 1 of 5 USSLB stages (8.6% stage I—olfactory bulb only; 15.4% IIa—brainstem predominant; 13.6% IIb—limbic predominant; 31.8% III—brainstem and limbic; and 30.7% IV—neocortical) yet using the Braak staging system 70 cases (25.3%) could not be classified. Those with USSLB stages III and IV died at a younger age. Multiple measures of motor parkinsonism, cognitive impairment, hyposmia, and probable RBD were significantly correlated with increasing USSLB stage. We conclude that the USSLB is the most comprehensive staging system for all Lewy body disorders and allows for categorization and ranking of all brains with significant correlations to many motor and nonmotor clinical signs and symptoms.

ABSTRACTBackgroundAbnormal color vision and contrast acuity may have significant impact on daily activities.ObjectiveEvaluate color visual acuity, at high and low contrast, in Parkinson's disease (PD) and controls using an iPad application.MethodsColor visual acuity was tested with the Variable Contrast Acuity Chart (King‐Devick Test LLC, Oakbrook Terrace, IL) on an iPad 2 at 40 cms using five colors (red, green, blue, yellow, and black) at low (2.5%) and high (100%) contrast. A numerical score (0–95) was assigned based on the number of correctly identified letters.ResultsThirty‐six PD (mean ± standard deviation age 68 ± 10 years) and 36 controls (72 ± 11.2 years) were studied. PD disease duration was 6.4 ± 4.6 years; MDS‐UPDRS part II was 11.7 ± 7.0, and part III was 24.5 ± 9.9. After adjusting for age and sex, PD patients had significantly (P < 0.05) lower scores at high (100%) as well as low (2.5%) contrast for all five colors tested (red, green, blue, yellow, and black), except yellow low contrast (2.5%; P = 0.10). The largest effect size (0.88) was with yellow high contrast, and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy using a cut‐off score of 82 was 31%, 97%, 92%, 58%, and 64%, respectively. No correlation to disease duration was found.ConclusionsThis iPad application may be a simple‐to‐use biomarker for assessing color vision in PD. Further research is needed to determine disease specificity and whether there is a role in monitoring disease progression, treatment response, and identifying prodromal PD.

Background: Some epidemiology studies suggest that atherosclerotic cardiovascular disease (ASCVD) risk factors increase the risk of developing Parkinson’s disease (PD). However, conflicting data suggest lower rates of ASCVD in PD. Objective: The objective of this study is to determine, with data from a longitudinal clinicopathological study, whether ASCVD risk factors are associated with a PD diagnosis and/or increased brain or peripheral load of Lewy-type synucleinopathy (LTS). Methods: All subjects were followed to autopsy and neuropathological examination in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Multivariable regression models, including age, gender, and smoking history, were used to investigate the association of a PD diagnosis or brain or submandibular gland LTS load with ASCVD risk factors. Results: 150 subjects were included (PD n = 60, controls n = 90). Univariable comparisons and regression models showed a general trend to inverse associations. The multivariable odds ratio (OR) of brain LTS load for carotid artery disease was 0.93 (95% CI: 0.86 to 0.98; p = 0.02), for anticoagulant use 0.95 (95% CI: 0.90 to 0.99; p = 0.04) and for abnormal heart weight 0.96 (95% CI: 0.92 to 0.99; p = 0.01). Composite clinical and overall (clinical + pathology composite risk scores) composite risk scores were also significantly lower in the PD subjects ( p = 0.0164 and 0.0187, respectively). Submandibular gland LTS load was not significantly related to ASCVD conditions. Conclusions: This study shows associations of higher brain LTS with lower prevalence of both clinical and pathological indices of ASCVD in PD subjects versus age-similar controls. We suggest that this is due to α-synuclein pathology-induced sympathetic denervation in PD.

Abstract Background Understanding the relationship between clinical and patient-reported outcomes (PROs) will help support clinical care and future clinical trial design of novel therapies for focal segmental glomerulosclerosis (FSGS). Methods FSGS patients ≥8 years of age enrolled in the Nephrotic Syndrome Study Network completed Patient-Reported Outcomes Measurement Information System PRO measures of health-related quality of life (HRQoL) (children: global health, mobility, fatigue, pain interference, depression, anxiety, stress and peer relationships; adults: physical functioning, fatigue, pain interference, sleep impairment, mental health, depression, anxiety and social satisfaction) at baseline and during longitudinal follow-up for a maximum of 5 years. Linear mixed-effects models were used to determine which demographic, clinical and laboratory features were associated with PROs for each of the eight children and eight adults studied. Results There were 45 children and 114 adult FSGS patients enrolled that had at least one PRO assessment and 519 patient visits. Multivariable analyses among children found that edema was associated with global health (−7.6 points, P = 0.02) and mobility (−4.2, P = 0.02), the number of reported symptoms was associated with worse depression (−2.7 per symptom, P = 0.009) and anxiety (−2.3, P = 0.02) and the number of emergency room (ER) visits in the prior 6 months was associated with worse mobility (−2.8 per visit, P &lt; 0.001) and fatigue (−2.4, P = 0.03). Multivariable analyses among adults found the number of reported symptoms was associated with worse function in all eight PROMIS measures and the number of ER visits was associated with worse fatigue, pain interference, sleep impairment, depression, anxiety and social satisfaction. Laboratory markers of disease severity (i.e. proteinuria, estimated glomerular filtration rate and serum albumin) did not predict PRO in multivariable analyses, with the single exception of complete remission and better pain interference scores among children (+9.3, P = 0.03). Conclusions PROs provide important information about HRQoL for persons with FSGS that is not captured solely by the examination of laboratory-based markers of disease. However, it is critical that instruments capture the patient experience and FSGS clinical trials may benefit from a disease-specific instrument more sensitive to within-patient changes.