Citations

Objective: To understand the challenges to diagnosis in patients with neurogenic orthostatic hypotension (nOH) Background: nOH is a sustained reduction in blood pressure (BP) with postural change associated with autonomic dysfunction. Despite symptoms of nOH, many patients struggle to find an accurate diagnosis. Methods: An online, US-based survey designed by the authors was conducted by Harris Poll. Eligible participants were ≥18 years of age with Parkinson disease, multiple system atrophy, or pure autonomic failure and ≥1 of the following: orthostatic hypotension (OH), nOH, low BP, OH/nOH symptoms, or were caregivers of eligible participants. Results: The survey included 363 patients and 128 caregivers. Groups were separate, where caregivers were not the caregivers to patient responders. Respondents indicated that patients experienced nOH symptoms long term (Table 1) . Most patients (69%) and caregivers (59%) reported discussing nOH symptoms with a healthcare provider (HCP) within the first year of symptom onset, but only 36% of patients and 16% of caregivers reported a formal diagnosis of OH or nOH. Of those with a formal diagnosis, the majority of patients (50%) were frustrated by the path to diagnosis and more than 40% of patients and caregivers reported that the patient saw ≥3 HCPs before diagnosis. After diagnosis, most patients (70%) and caregivers (60%) reported improved symptom management. Conclusions: This survey reveals that patients and caregivers may find the path to nOH diagnosis challenging and suggests increased awareness among HCPs is needed. Once a diagnosis is made nOH symptoms are better managed.

Aims The outcomes of patients presenting with acute myocarditis and life‐threatening ventricular arrhythmias (LT‐VA) are unclear. The aim of this study was to assess the incidence and predictors of recurrent major arrhythmic events (MAEs) after hospital discharge in this patient population. Methods and results We retrospectively analysed 156 patients (median age 44 years; 77% male) discharged with a diagnosis of acute myocarditis and LT‐VA from 16 hospitals worldwide. Diagnosis of myocarditis was based on histology or the combination of increased markers of cardiac injury and cardiac magnetic resonance (CMR) Lake Louise criteria. MAEs were defined as the relapse, after discharge, of sudden cardiac death or successfully defibrillated ventricular fibrillation, or sustained ventricular tachycardia (sVT) requiring implantable cardioverter‐defibrillator therapy or synchronized external cardioversion. Median follow‐up was 23 months [first to third quartile (Q1–Q3) 7–60]. Fifty‐eight (37.2%) patients experienced MAEs after discharge, at a median of 8 months (Q1–Q3 2.5–24.0 months; 60.3% of MAEs within the first year). At multivariable Cox analysis, variables independently associated with MAEs were presentation with sVT [hazard ratio (HR) 2.90, 95% confidence interval (CI) 1.38–6.11]; late gadolinium enhancement involving ≥2 myocardial segments (HR 4.51, 95% CI 2.39–8.53), and absence of positive short‐tau inversion recovery (STIR) (HR 2.59, 95% CI 1.40–4.79) at first CMR. Conclusions Among patients discharged with a diagnosis of myocarditis and LT‐VA, 37.2% had recurrences of MAEs during follow‐up. Initial CMR pattern and sVT at presentation stratify the risk of arrhythmia recurrence.

Recent reports have suggested a high prevalence of olfactory bulb synucleinopathy in Lewy body disorders but there have been no estimates of the sensitivity or specificity of this as a diagnostic test. We performed α‐synuclein immunostaining on paraffin‐embedded sections of olfactory bulb from a series of neuropathologically‐diagnosed subjects from the Sun Health Research Institute Brain Donation Program/Arizona Parkinson's Disease Consortium. Included in the series were 76 normal elderly individuals, 8 subjects with incidental Lewy body disease (ILBD), 63 with Parkinson's disease (PD) and 79 with dementia with Lewy bodies (DLB). Sections were stained with a sensitive method employing pretreatment with proteinase K. The ratios of positive to negative olfactory bulb staining for each diagnostic category were: normal 5/71; ILBD 8/0; PD 57/6; DLB 74/5. An α‐synuclein‐positive olfactory bulb has 92% sensitivity and 93% specificity for the diagnosis of PD versus normal while for DLB it is 94% and 93%, respectively. As all 8 cases of ILBD had a positive olfactory bulb it appears that olfactory bulb synucleinopathy may also be a reliable marker of presymptomatic Lewy body disorders. Supported by the AZ Dept. of Health Services, NIA P30 AG19610 and the Prescott Family Initiative of the Michael J. Fox Foundation.

Background: Braak and others have proposed that Lewy-type α-synucleinopathy in Parkinson’s disease (PD) may arise from an exogenous pathogen that passes across the gastric mucosa and then is retrogradely transported up the vagus nerve to the medulla. Objective: We tested this hypothesis by immunohistochemically staining, with a method specific for p-serine 129 α-synuclein (pSyn), stomach and vagus nerve tissue from an autopsy series of 111 normal elderly subjects, 33 with incidental Lewy body disease (ILBD) and 53 with PD. Methods: Vagus nerve samples were taken adjacent to the carotid artery in the neck. Stomach samples were taken from the gastric body, midway along the greater curvature. Formalin-fixed paraffin-embedded sections were immunohistochemically stained for pSyn, shown to be highly specific and sensitive for α-synuclein pathology. Results: Median disease duration for the PD group was 13 years. In the vagus nerve none of the 111 normal subjects had pSyn in the vagus, while 12/26 ILBD (46%) and 32/36 PD (89%) subjects were pSyn-positive. In the stomach none of the 102 normal subjects had pSyn while 5/30 (17%) ILBD and 42/52 (81%) of PD subjects were pSyn-positive. Conclusion: As there was no pSyn in the vagus nerve or stomach of subjects without brain pSyn, these results support initiation of pSyn in the brain. The presence of pSyn in the vagus nerve and stomach of a subset of ILBD cases indicates that synucleinopathy within the peripheral nervous system may occur, within a subset of individuals, at preclinical stages of Lewy body disease.

Background Patients with restless legs syndrome (RLS) have increased silent microvascular disease by magnetic resonance imaging. However, there has been no previous autopsy confirmation of these magnetic resonance imaging findings. RLS is also frequently associated with inflammatory and immunologically mediated medical disorders. The postmortem cortex in patients with RLS was therefore evaluated for evidence of microvascular and immunological changes. Methods and Results Ten microvascular injury samples of precentral gyrus in 5 patients with RLS (3 men, 2 women; mean age, 81 years) and 9 controls (2 men, 7 women; mean age, 90 years) were studied by hematoxylin and eosin stains in a blinded fashion. None of the subjects had a history of stroke or neurologic insults. In a similar manner, the following immunohistochemistry stains were performed: (1) glial fibrillary acidic protein (representing gliosis, reactive change of glial cells in response to damage); (2) CD3 (a T‐cell marker); (3) CD19 (a B‐cell marker); (4) CD68 (a macrophage marker); and (5) CD117 (a mast cell marker). Patients with RLS had significantly greater silent microvascular disease ( P =0.015) and gliosis ( P =0.003). T cells were increased in RLS compared with controls ( P =0.009) and tended to colocalize with microvascular disease ( P =0.003). Other markers did not differ. There was no correlation between microvascular lesion load and RLS severity or duration. Conclusions Patients with RLS had statistically significantly more silent cerebral microvascular disease and gliosis than controls compatible with previous magnetic resonance imaging studies and with studies showing a link between RLS and hypertension, clinical stroke, and cardiovascular disease. T‐cell invasion may be a secondary phenomenon.

Abstract Background and study aims Proton pump inhibitors (PPI) are effective medical therapy options for gastro-esophageal reflux disease (GERD). However, 20 % to 40 % of patients report symptoms despite taking daily PPI. Transoral incisionless fundoplication (TIF2) and magnetic sphincter augmentation (MSA) are less invasive options for the treatment of refractory GERD and are increasingly gaining popularity. Methods We conducted a comprehensive search of several databases to identify relevant studies. Our primary aim was to compare the efficacy of both interventions reported as improvement in Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) score, overall patient satisfaction, improvement in post-procedure regurgitation, and fraction of patients completely off PPI therapy at follow up. Results Twenty-four studies with 1942 patients were included in the final analysis. Both MSA and TIF2 had comparable technical success and clinical success based on improvement in GERD-HRQL scores i. e. 98.8 % (CI 95.6,99.7) vs 98.5 % (CI 95.7,99.5) and 80.4 % (CI 66,89.6) vs 77.7 % (CI 64.1,87.2), respectively. A significantly greater proportion of patients reported improvement in regurgitation, i. e. 91.1 % (CI 83.8,95.3) vs 73.1 % (CI 62.5,81.7) and were able to completely discontinue PPI therapy with MSA compared to TIF2 i. e. 91.3 % (CI 81.5,96.2) vs 63.8 % (CI 51.6,74.4). Patients’ BMI and presence of a hiatal hernia did not have any effect on procedural outcomes. Conclusion Both procedures performed at par when comparing clinical success in terms of improvement in GERD-HRQL scores. In terms of overall patient satisfaction, post procedure regurgitation and cumulative number of patients off PPI therapy, MSA outperforms TIF2.

Abstract Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level. It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions. Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered. In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis. Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice.

Background: Left atrial appendage (LAA) occlusion provides an alternative to oral anticoagulation for thromboembolic risk reduction in patients with nonvalvular atrial fibrillation. Since regulatory approval in 2015, the WATCHMAN device has been the only LAA closure device available for clinical use in the United States. The PINNACLE FLX study (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology) evaluated the safety and effectiveness of the next-generation WATCHMAN FLX LAA closure device in patients with nonvalvular atrial fibrillation in whom oral anticoagulation is indicated, but who have an appropriate rationale to seek a nonpharmaceutical alternative. Methods: This was a prospective, nonrandomized, multicenter US Food and Drug Administration study. The primary safety end point was the occurrence of one of the following events within 7 days after the procedure or by hospital discharge, whichever was later: death, ischemic stroke, systemic embolism, or device- or procedure-related events requiring cardiac surgery. The primary effectiveness end point was the incidence of effective LAA closure (peri-device flow ≤5 mm), as assessed by the echocardiography core laboratory at 12-month follow-up. Results: A total of 400 patients were enrolled. The mean age was 73.8±8.6 years and the mean CHA 2 DS 2 -VASc score was 4.2±1.5. The incidence of the primary safety end point was 0.5% with a 1-sided 95% upper CI of 1.6%, meeting the performance goal of 4.2% ( P <0.0001). The incidence of the primary effectiveness end point was 100%, with a 1-sided 95% lower CI of 99.1%, again meeting the performance goal of 97.0% ( P <0.0001). Device-related thrombus was reported in 7 patients, no patients experienced pericardial effusion requiring open cardiac surgery, and there were no device embolizations. Conclusions: LAA closure with this next-generation LAA closure device was associated with a low incidence of adverse events and a high incidence of anatomic closure. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02702271.

AbstractBackgroundHyposmia is characteristic of idiopathic Parkinson's disease (PD) and dementia with Lewy bodies (DLBs), whereas progressive supranuclear palsy (PSP) typically has normal sense of smell. However, there is a lack of pathologically confirmed data.ObjectiveThe objective is to study hyposmia in pathologically confirmed PSP patients and compare to PD patients and nondegenerative controls.MethodsWe studied autopsied subjects in the Arizona Study of Aging and Neurodegenerative Disorders who had antemortem olfactory testing and a neuropathological diagnosis of either PD, PSP, or control.Results: This study included 281 cases. Those with neuropathologically confirmed PSP (N = 24) and controls (N = 174) had significantly better sense of smell than those with PD (N = 76). Although most PSP patients had normal olfaction, there were some with hyposmia, resulting in an overall reduced sense of smell in PSP compared to controls. The sensitivity of having PSP pathologically in those presenting with parkinsonism and normosmia was 93.4% with a specificity of 64.7%. Cases with both PSP and PD pathologically had reduced sense of smell similar to PD alone (N = 7). Hyposmic PSP patients had significantly higher Lewy body burden not meeting criteria for additional PD/DLB diagnosis.ConclusionsPathologically confirmed PD had reduced olfaction compared with PSP or controls. In the setting of parkinsonism in this sample, the presence of normosmia had high sensitivity for PSP. Hyposmia in PSP suggests the presence of additional Lewy body pathology. © 2021 International Parkinson and Movement Disorder Society