Citations

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.

Abstract Introduction A phase 2b clinical trial, HEADWAY‐DLB, was performed to assess treatment with intepirdine, a serotonin receptor antagonist, in patients with dementia with Lewy bodies (DLB). Methods HEADWAY‐DLB was a multinational, double‐blind, randomized, placebo‐controlled study. Two hundred sixty‐nine DLB patients were randomized to receive placebo, 70 mg/day intepirdine, or 35 mg/day intepirdine over 24 weeks. The primary endpoint was change from baseline to week 24 on the Unified Parkinson's Disease Rating Scale–Part III (UPDRS‐III). Results Both intepirdine groups did not demonstrate significant benefits over placebo at 24 weeks on the UPDRS‐III (35 mg/day: P = .1580, 70 mg/day: P = .6069). All other endpoints were not significant. Intepirdine was well tolerated, with a slightly higher incidence of gastrointestinal adverse events observed in the intepirdine groups versus placebo. Discussion Intepirdine treatment did not lead to improvements over placebo in patients with DLB. As one of the largest DLB studies to date, HEADWAY‐DLB demonstrates that international trials for DLB are feasible within a reasonable timeframe.

Summary: Advances in virtual surgical planning and three-dimensionally–printed guides have enabled increased precision in vascularized free fibula flap reconstruction of the mandible and valuable preoperative planning. However, virtual surgical planning currently requires high-resolution computed tomographic scans, exposing patients to ionizing radiation. The aim of this study was to determine whether black bone magnetic resonance imaging can be used for accurate surgical planning and three-dimensionally–printed guide creation, thus reducing patient radiation exposure. This study included 10 cadaver heads and 10 cadaver lower extremities. A mock fibula free flap for mandible reconstruction was performed. Five operations were planned with guides created using black bone magnetic resonance imaging, whereas the other five were planned and performed using guides created with computed tomographic scan data. All specimens underwent a postoperative computed tomographic scan, and three-dimensional reconstruction of scans was performed and surgical accuracy to the planned surgery was assessed. Guides created from black bone magnetic resonance imaging demonstrated high accuracy to the surgical plan. There was no statistically significant difference in postoperative deviation from the plan when black bone magnetic resonance imaging versus computed tomographic scanning was used for virtual surgical planning and guide creation. Both modalities led to a postoperative positive or negative deviation from the virtual plan within 0.8 mm. This study demonstrates that virtual surgical planning and three-dimensionally–printed guide creation for free fibula flaps for mandible reconstruction can be performed using black bone magnetic resonance imaging with comparable accuracy to computed tomographic scanning. This could reduce radiation exposure for patients and enable a more streamlined imaging process for head and neck cancer patients.

Precis: Diplopia was present in ~20% of patients with Ahmed FP7 (FP7) or Baerveldt 350 (B350), compared with 5% to 6% in those with Baerveldt 250 (B250) or controls, suggesting risk of diplopia should be included in preoperative counseling. Purpose: The purpose of this study was to examine the prevalence of diplopia and strabismus in patients with B250, B350, or FP7 glaucoma drainage devices (GDD). Materials and Methods: In this cohort study, glaucoma patients 18 years and above who had received, or would be receiving, a B250, B350, or FP7 GDD, and medically treated controls were consecutively enrolled from August 8, 2017, through July 31, 2019. The Diplopia Questionnaire was administered ≥30 days postoperatively, and upon enrollment to the controls. All diplopic patients underwent orthoptic measurements, which were reviewed by a strabismus specialist. Patients with GDDs in quadrants other than superotemporal, multiple GDDs, or scleral buckles were excluded. Bonferroni correction was applied for pairwise comparisons. Results: Diplopia was reported in 23/129 (17.8%) GDD patients and 5/99 (5.1%) control patients (P=0.003): 8/35 (22.9%) FP7, 2/32 (6.3%) B250, and 13/62 (21.0%) B350, with significant differences between FP7 versus controls (P=0.014) and B350 versus controls (P=0.011). Diplopia was attributable to GDD in 2 FP7 (5.9%, 95% confidence interval: 0.7-19.2), 0 B250, and 4 B350 (6.5%, 95% confidence interval: 1.7-15.2) patients, without significant differences between the GDDs. Conclusions: Patients with the larger (B350) or the higher profile plate (FP7) GDDs were more likely to experience diplopia than controls, and diplopia was attributable to the GDD in ~6% of patients with either a FP7 or a B350 GDD. Since diplopia can affect patients’ quality of life, preoperative counseling for GDD surgery, particularly B350 and FP7, should include a discussion of the risk of diplopia.

Background: Imaging biomarkers have the potential to distinguish between different brain pathologies based on the type of ligand used with PET. AV-45 PET (florbetapir, Amyvid™) is selective for the neuritic plaque amyloid of Alzheimer’s disease (AD), while AV-133 PET (florbenazine) is selective for VMAT2, which is a dopaminergic marker. Objective: To report the clinical, AV-133 PET, AV-45 PET, and neuropathological findings of three clinically diagnosed dementia patients who were part of the Avid Radiopharmaceuticals AV133-B03 study as well as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Methods: Three subjects who had PET imaging with both AV-133 and AV-45 as well as a standardized neuropathological assessment were included. The final clinical, PET scan, and neuropathological diagnoses were compared. Results: The clinical and neuropathological diagnoses were made blinded to PET scan results. The first subject had a clinical diagnosis of dementia with Lewy bodies (DLB); AV-133 PET showed bilateral striatal dopaminergic degeneration, and AV-45 PET was positive for amyloid. The final clinicopathological diagnosis was DLB and AD. The second subject was diagnosed clinically with probable AD; AV-45 PET was positive for amyloid, while striatal AV-133 PET was normal. The final clinicopathological diagnosis was DLB and AD. The third subject had a clinical diagnosis of DLB. Her AV-45 PET was positive for amyloid and striatal AV-133 showed dopaminergic degeneration. The final clinicopathological diagnosis was multiple system atrophy and AD. Conclusion: PET imaging using AV-133 for the assessment of striatal VMAT2 density may help distinguish between AD and DLB. However, some cases of DLB with less-pronounced nigrostriatal dopaminergic neuronal loss may be missed.

Précis: In this longitudinal study of patients with open-angle (OAG), pseudoexfoliative (PXE), or neovascular glaucoma (NVG) receiving glaucoma drainage devices (GDD), posttube cumulative rates of reoperation, corneal graft, and visually threatening complications (VT-complications) increased beyond 5 years and were not significantly affected by glaucoma type. Purpose: To study the need for additional glaucoma surgery and development of complications after first GDD surgery in eyes with primary OAG, PXE, or NVG glaucoma. Patients and Methods: There were 306 eyes with OAG (n=185), PXE (n=60), or NVG (n=61) glaucoma who received a first GDD between 1996 and 2017. Outcomes including glaucoma reoperation, corneal graft procedure, and VT-complications after GDD were measured. Kaplan-Meier analysis was used to compare cumulative rate of reaching outcomes over time after GDD placement among the 3 glaucoma groups. Results: When comparing the OAG, PXE, and NVG groups, there were no significant differences in post-GDD cumulative rates of reoperation (P=0.33), corneal graft (P=0.26), or VT-complications (P=0.65) over time. For all eyes, the overall cumulative rates for each outcome measure increased beyond 5 years, and specific Kaplan-Meier rates (5-y, 10-y) included: reoperation (16%, 25%), corneal graft (6%, 12%), VT-complications (9%, 14%). When comparing specific GDDs, the Ahmed FP7 had a higher cumulative reoperation rate over time compared with the Baerveldt 350 (P=0.019). Conclusion: Glaucoma type did not significantly affect post-GDD cumulative rates of reoperation, corneal graft, and VT-complication among the OAG, PXE, and NVG groups. For all eyes, cumulative rates of reoperation, corneal graft, and VT-complications increased beyond 5 years. The Ahmed FP7 had a significantly higher cumulative reoperation rate compared with the Baerveldt 350 over time.

AbstractBackgroundChange in left atrial pressure (LAP) has been shown to be associated with symptom improvement post‐MitraClip; however, the association between acute procedural changes in transmitral diastolic mean gradient (MG) compared to LAP and symptom improvement is not well established.Methods164 consecutive patients undergoing MitraClip at Mayo Clinic between June 2014 and May 2018 were included. Preclip and postclip MG and LAP were recorded. Baseline demographics, clinical, and echocardiographic outcomes, including 30‐day New York Heart Association (NYHA) functional status were obtained from patient charts.ResultsMedian age was 81.5 years (IQR: 76.3, 87), 34% were female and 94.5% had NYHA class III and IV functional status at baseline. At baseline, median MG was 4 mmHg (IQR: 3, 5) and LAP was 19 mmHg (IQR: 16, 23.5). Following MitraClip deployment, the median MG was 4 mmHg (IQR: 3, 6) and the median LAP was 17 mmHg (IQR: 14, 21), 69.5% of patients had less than moderate MR. There was no statistically significant association between change in MG and NYHA functional class at 30 days (OR = 0.95, 95% CI: 0.76–1.20). However, a reduction in LAP following MitraClip deployment was significantly associated with improvement in NYHA functional status at 30 days following adjustments for age and sex (aOR 3.36, 95% CI: 1.34–8.65). There was no significant correlation between change in mean LAP and change in MG (p = .98).ConclusionUnlike change in left atrial pressure, change in MG post‐MitraClip was not associated with patient reported outcomes at 30 days and did not correlate with change in left atrial pressure. Long‐term follow up is needed to evaluate the impact of LA pressure on symptoms.