Peripheral nervous system manifestations of MOG antibody associated disease.

Recent studies have reported the involvement of peripheral nervous system (PNS) in association with MOG-IgG, including isolated neuropathies. In this retrospective study we characterized the PNS involvement in MOG antibody associated disease (MOGAD). Six out of 215 MOGAD patients had PNS involvement (all polyradiculopathy) that occurred concurrently with a CNS demyelinating episode. We also demonstrated MOG expression in healthy human controls' proximal nerve root. Nine patients with true-positive MOG-IgG1 had PNS involvement temporally unrelated to a CNS demyelinating event. All these patients had an alternate etiology of PNS involvement. Isolated peripheral neuropathy is not a feature of MOGAD, but inflammatory nerve root involvement can occur concurrently with CNS demyelinating events.

A Multimodality Imaging Approach to Defining Risk in Patients With Acute Pulmonary Embolism.

BACKGROUND: Morbidity and mortality for acute pulmonary embolism (PE) remain high. Therapies such as catheter-directed thrombolysis may improve outcomes, but these are generally reserved for higher-risk patients. Imaging may help guide the use of the newer therapies, but current guidelines focus more on clinical factors. Our goal was to create a risk model that incorporated quantitative echocardiographic and computed tomography (CT) measures of right ventricular (RV) size and function, thrombus burden, and serum biomarkers of cardiac overload or injury. METHODS: This was a retrospective study of 150 patients evaluated by a PE response team. Echocardiography was performed within 48 hours of diagnosis. Computed tomography measures included RV/left ventricular (LV) ratio and thrombus load (Qanadli score). Echocardiography was used to obtain various quantitative measures of RV function. We compared characteristics of those who met the primary endpoint (7-day mortality and clinical deterioration) to those who did not. Receiver operating curve analysis was used to assess the performance of different combinations of clinically relevant features and the association with adverse outcomes. RESULTS: Fifty-two percent of patients were female, with age 62 ± 17 years, systolic blood pressure 123 ± 25 mm Hg, heart rate 98 ± 19, troponin 3.2 ± 35 ng/dL, and b-type natriuretic peptide (BNP) 467 ± 653. Fourteen (9.3%) were treated with systemic thrombolytics, 27 (18%) underwent catheter-directed thrombolytics, 23 (15%) were intubated or required vasopressors, and 14 (9.3%) died. Patients who met the primary endpoint (44%) versus those who did not (56%) had lower RV S' (6.6 vs 11.9 cm/sec; P < .001) and RV free wall strain (-10.9% vs -13.6%; P = .005), higher RV/LV ratio on CT, and higher serum BNP and troponin levels. Receiver operating curve analysis demonstrated an area under the curve of 0.89 for a model that included RV S', RV free wall strain and tricuspid annular plane systolic excursion/RV systolic pressure ratio from echo, thrombus load and RV/LV ratio from CT, and troponin and BNP levels. CONCLUSION: A combination of clinical, echo, and CT findings that reflect the hemodynamic effects of the embolism identified patients with adverse events related to acute PE. Optimized scoring systems that focus on reversible abnormalities attributable to PE may allow more appropriate triaging of intermediate- to high-risk patients with PE for early interventional strategy.

Group augmentation underlies the evolution of complex sociality in the face of environmental instability.

Although kin selection is assumed to underlie the evolution of sociality, many vertebrates-including nearly half of all cooperatively breeding birds-form groups that also include unrelated individuals. Theory predicts that despite reducing kin structure, immigration of unrelated individuals into groups can provide direct, group augmentation benefits, particularly when offspring recruitment is insufficient for group persistence. Using population dynamic modeling and analysis of long-term data, we provide clear empirical evidence of group augmentation benefits favoring the evolution and maintenance of complex societies with low kin structure and multiple reproductives. We show that in the superb starling (Lamprotornis superbus)-a plural cooperative breeder that forms large groups with multiple breeding pairs, and related and unrelated nonbreeders of both sexes-offspring recruitment alone cannot prevent group extinction, especially in smaller groups. Further, smaller groups, which stand to benefit more from immigration, exhibit lower reproductive skew for immigrants, suggesting that reproductive opportunities as joining incentives lead to plural breeding. Yet, despite a greater likelihood of becoming a breeder in smaller groups, immigrants are more likely to join larger groups where they experience increased survivorship and greater reproductive success as breeders. Moreover, immigrants form additional breeding pairs, increasing future offspring recruitment into the group and guarding against complete reproductive failure in the face of environmental instability and high nest predation. Thus, plural breeding likely evolves because the benefits of group augmentation by immigrants generate a positive feedback loop that maintains societies with low and mixed kinship, large group sizes, and multiple reproductives.

Frequency of Asymptomatic Optic Nerve Enhancement in a Large Retrospective Cohort of Patients With Aquaporin-4+ NMOSD.

BACKGROUND AND OBJECTIVES: Asymptomatic or persistent optic nerve enhancement in aquaporin-4 (AQP4)-immunoglobulin G (IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) is thought to be rare. Improved understanding may have important implications for assessment of treatment efficacy in clinical trials and in clinical practice. Our objective was to characterize NMOSD interattack optic nerve enhancement. METHODS: This was a retrospective cohort study performed between 2000 and 2019 (median follow-up 5.5 [range 1-35] years) of patients with AQP4-IgG-positive optic neuritis (ON) evaluated at Mayo Clinic. MRI orbits were reviewed by a neuroradiologist, neuro-ophthalmologist, and neuroimmunologist blinded to the clinical history. Interattack optic nerve enhancement (>30 days after attack) was measured. The correlation between interattack enhancement and Snellen visual acuity (VA), converted to logarithm of the minimum angle of resolution (logMAR), at attack and at follow-up were assessed. RESULTS: A total of 198 MRI scans in 100 patients with AQP4-IgG+ NMOSD were identified, with 107 interattack MRIs from 78 unique patients reviewed. Seven scans were performed before any ON (median 61 days before attack [range 21-271 days]) and 100 after ON (median 400 days after attack [33-4,623 days]). Optic nerve enhancement was present on 18/107 (16.8%) interattack scans (median 192.5 days from attack [33-2,943]) of patients with preceding ON. On 15 scans, enhancement occurred at the site of prior attacks; the lesion location was unchanged, but the lesion length was shorter. Two scans (1.8%) demonstrated new asymptomatic lesions (prior scan demonstrated no enhancement). In a third patient with subjective blurry vision, MRI showed enhancement preceding detectable eye abnormalities on examination noted 15 days later. There was no difference in VA at preceding attack nadir (logMAR VA 1.7 vs 2.1; p = 0.79) or long-term VA (logMAR VA 0.4 vs 0.2, p = 0.56) between those with and without interattack optic nerve enhancement. DISCUSSION: Asymptomatic optic nerve enhancement occurred in 17% of patients with NMOSD predominantly at the site of prior ON attacks and may represent intermittent blood-brain barrier breakdown or subclinical ON. New asymptomatic enhancement was seen only in 2% of patients. Therapeutic clinical trials for NMOSD require blinded relapse adjudication when assessing treatment efficacy, and it is important to recognize that asymptomatic optic nerve enhancement can occur in patients with ON.

Use of activPAL to Measure Physical Activity in Community-Dwelling Older Adults: A Systematic Review.

Objective: To perform a systematic review of the literature to describe how the activPAL accelerometer has been used to measure physical activity (PA) in community-dwelling older adults to standardize collection of PA data in this population using this thigh-worn accelerometer. Data Sources: A comprehensive search of the following databases was completed: Cumulative Index to Nursing and Allied Health Complete, Embase, OVID Medicine, PubMed/Web of Science, and Scopus. Study Selection: Studies were included if published before August 1, 2020, were written in English, and used activPAL to measure PA in community-dwelling, noninstitutionalized adults 65 years or older. Titles and abstracts were independently reviewed, and the decision to include or exclude was made by 100% consensus. Data Extraction: Three research team members independently extracted the data from included studies. Extracted data were compared and discussed with relevant information included. Study quality was assessed using the Quality Assessment Tool for Observational Cohort and Cross-sectional Studies. Data Synthesis: A total of 7 articles met the inclusion criteria. Three of the 7 studies used activPAL to report steps/d, ranging from 864-15847 steps/d. Time spent stepping or walking was reported by 4 studies using various units. Sit-to-stand transitions were reported by 4 studies, averaging 10-63 transitions/d. Sedentary time was assessed in 6 studies, whereas moderate to vigorous physical activity was not measured using activPAL in any study. Conclusions: The activPAL is most often used to collect data on step count and walking, sit-to-stand transitions, and sedentary time in community-dwelling older adults.

Prenatal environmental conditions underlie alternative reproductive tactics that drive the formation of a mixed-kin cooperative society.

Although animal societies often evolve due to limited natal dispersal that results in kin clustering and facilitates cooperation among relatives, many species form cooperative groups with low kin structure. These groups often comprise residents and immigrants of the same sex that compete for breeding opportunities. To understand how these mixed-kin societies form, we investigated the causes and fitness consequences of dispersal decisions in male cooperatively breeding superb starlings (Lamprotornis superbus) inhabiting a climatically unpredictable environment. We show that the two alternative reproductive tactics-natal dispersal or philopatry-exhibit reproductive trade-offs resulting in equivalent lifetime inclusive fitness. Unexpectedly, an individual's tactic is related to the prenatal environment its parents experience before laying rather than the environment it experiences as a juvenile. Individuals that adopt the tactic not predicted by prenatal environmental conditions have lower fitness. Ultimately, climate-driven oscillating selection appears to stabilize mixed-kin societies despite the potential for social conflict.

Optic chiasm involvement in AQP-4 antibody-positive NMO and MOG antibody-associated disorder.

BACKGROUND: Optic neuritis (ON) is often the presenting symptom in inflammatory central nervous system demyelinating disorders. OBJECTIVE: To compare the frequency and pattern of optic chiasm involvement in patients with aquaporin-4-immunoglobulin G (AQP4-IgG)-associated ON to patients with myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG)-associated ON. METHODS: Retrospective review of all patients evaluated at Mayo Clinic, Stanford University and Ramathibodi Hospital who were found to have: (1) ON, (2) either MOG-IgG or AQP4-IgG by cell-based assay, and (3) magnetic resonance imaging (MRI) at the time of ON. MRI was reviewed for contrast enhancement of the optic chiasm and the pattern of involvement. RESULTS: One hundred and fifty-four patients (74 AQP4-IgG and 80 MOG-IgG) were included. Among patients with AQP4-IgG-ON, 20% had chiasmal involvement, compared with 16% of patients with MOG-IgG-ON (p = 0.66). In patients with chiasmal involvement, longitudinally extensive optic nerve enhancement (from orbit extending to chiasm) was identified in 54% of MOG-IgG-ON patients, compared with 7% of AQP4-IgG-ON patients (p = 0.01). CONCLUSION: Chiasmal involvement of MOG-IgG-ON and AQP4-IgG-ON occur at more similar frequencies than previously reported. Furthermore, MOG-IgG-ON chiasmal involvement is more likely to be part of a longitudinally extensive optic nerve lesion.

Population-Based Epidemiology Study of Paraneoplastic Neurologic Syndromes.

OBJECTIVES: Population-based epidemiologic data for paraneoplastic neurologic syndromes (PNSs) in the United States are lacking. Our objective was to evaluate the incidence, prevalence, and associated morbidity of PNS. METHODS: We performed a population-based epidemiology study in Olmsted County, Minnesota, with patients identified between January 1, 1987, and December 31, 2018, using the medical records linkage system of the Rochester Epidemiology Project (REP) who met the definite/probable 2021 PNS criteria and 2004 PNS criteria. Patients with dermatomyositis and myasthenia gravis with underlying tumors were included. Age- and sex-specific population counts were obtained from REP resources for January 1, 2014 (prevalence denominator) and annually for 1987-2018 (incidence denominator). Morbidity was estimated using disability-adjusted life years (DALYs; years lived with disability [YLD] plus years of life lost [YLL]). RESULTS: There were 28 patients with PNS identified (50% female) residing in Olmsted County, Minnesota, with median age at diagnosis of 54.5 (IQR 46.5-69.0) years. All patients had a cancer diagnosis, and 18 (64%) patients were neural autoantibody positive including antineuronal nuclear autoantibody type 1 (ANNA-1/anti-Hu; n = 1), ANNA-2/anti-Ri (n = 1), muscle-type acetylcholine receptor (AChR; n = 6), Purkinje cell cytoplasmic antibody type 1 (PCA-1/anti-Yo; n = 1), kelch-like protein 11 (KLH11; n = 3), collapsin response mediator protein 5 (CRMP-5/anti-CV2; n = 2), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (n = 1), neurofilament light chain (n = 1), leucine zipper 4 (LUZP4; n = 1), and unclassified neural antibodies (n = 1). PNS incidence was 0.6/100,000 person-years and increased over time from 0.4/100,000 person-years (1987-2002) to 0.8/100,000 person-years (2003-2018) (p = 0.06). Prevalence was 5.4/100,000 people. The median follow-up period after PNS diagnosis was 3.1 years (IQR, 1.1-9.9 years). Total disability-adjusted life years (DALYs) for 28 patients with PNS were 472.7 years, based on total years of life lost (YLL) for patients dying between 1987 and 2018 (n = 15) of 445.3 years plus years lived with disability (YLD) 27.4 years. DISCUSSION: PNSs are rare neurologic disorders but are associated with severe morbidity and mortality. The estimated number of prevalent PNS cases in the United States is 17,099, and predicted DALY for all US PNS cases is 292,393 years. Their apparent increasing rate of detection is attributable to increasing physician awareness and availability of serologic testing.

Dual ankyrinG and subpial autoantibodies in a man with well-controlled HIV infection with steroid-responsive meningoencephalitis: A case report.

Neuroinvasive infection is the most common cause of meningoencephalitis in people living with human immunodeficiency virus (HIV), but autoimmune etiologies have been reported. We present the case of a 51-year-old man living with HIV infection with steroid-responsive meningoencephalitis whose comprehensive pathogen testing was non-diagnostic. Subsequent tissue-based immunofluorescence with acute-phase cerebrospinal fluid revealed anti-neural antibodies localizing to the axon initial segment (AIS), the node of Ranvier (NoR), and the subpial space. Phage display immunoprecipitation sequencing identified ankyrinG (AnkG) as the leading candidate autoantigen. A synthetic blocking peptide encoding the PhIP-Seq-identified AnkG epitope neutralized CSF IgG binding to the AIS and NoR, thereby confirming a monoepitopic AnkG antibody response. However, subpial immunostaining persisted, indicating the presence of additional autoantibodies. Review of archival tissue-based staining identified candidate AnkG autoantibodies in a 60-year-old woman with metastatic ovarian cancer and seizures that were subsequently validated by cell-based assay. AnkG antibodies were not detected by tissue-based assay and/or PhIP-Seq in control CSF (N = 39), HIV CSF (N = 79), or other suspected and confirmed neuroinflammatory CSF cases (N = 1,236). Therefore, AnkG autoantibodies in CSF are rare but extend the catalog of AIS and NoR autoantibodies associated with neurological autoimmunity.

Impact of Active Esophageal Cooling on Fluoroscopy Usage During Left Atrial Ablation.

Risks to collateral structures exist with radiofrequency (RF) ablation of the left atrium to obtain pulmonary vein isolation (PVI) for the treatment of atrial fibrillation. Passive luminal esophageal temperature (LET) monitoring is commonly utilized, but increasing data suggest limited benefits with LET monitoring. In contrast, active cooling of the esophagus has been shown to significantly reduce esophageal injury. Active cooling of the esophagus also avoids the need for stopping and repositioning an LET probe during use, which may reduce the need for fluoroscopy use. This study aimed to measure the impact on fluoroscopy use during RF ablation with esophageal cooling using a dedicated cooling device in a low-fluoroscopy practice. All patients who underwent PVI over a one-year timeframe by a single provider were analyzed. Patients undergoing PVI prior to the incorporation of an esophageal cooling protocol into standard ablation practice were treated with traditional LET monitoring. Patients treated after this point received active esophageal cooling, in which no LET monitoring is utilized. A total of 280 patients were treated; 91 patients were treated using LET monitoring, and 189 patients were treated with esophageal cooling. The mean total fluoroscopy time before the implementation of the esophageal cooling protocol in 91 patients was 194 seconds [standard deviation (SD): 182 seconds] per case, with a median of 144 seconds. The mean total fluoroscopy time after implementation in 189 patients was 126 seconds (SD: 120 seconds) per case with a median of 96 seconds, representing a reduction of 35% per case (p < 0.0001, Mann-Whitney U test). In this largest study to date of active esophageal cooling during PVI, a 35% reduction in fluoroscopy time compared with patients who received LET monitoring was found. This reduction was seen despite an already low fluoroscopy usage rate in place.

Functional Limitations and Perceived Neighborhood Walkability Among Urban Dwelling Older Adults.

Older adults with functional limitations (FLs) often experience obstacles to walking. Although health promotion programs targeting physical activity are available in lower-income areas, few studies have compared the walking experiences of older adults who have FLs with those who do not in the community. The purpose of this cross-sectional survey was to compare perceptions of neighborhood walkability among older adults living in lower-income communities with and without FLs. Participants (N = 132) were recruited in 2018 at regional health clinics in Flint, Michigan. To be eligible, participants had to be 65 years of age or older, report no cognitive decline, and be Flint residents. Of the 132 participants, the mean age was 69.74 (SD = 4.97). The majority were female (66%); African American (77%); single, divorced, or widowed (72%); educated below the General Education Development level (57%), and had a FL (67%). Older adults with FLs were significantly (p < 0.05) less likely than those without to visit many places within walking distance, to have well-lit neighborhoods at night, and to reside in neighborhoods where sidewalks were separated from the road and traffic. Multiple regression analyses revealed that having a FL was associated with poorer neighborhood perceptions of mixed-land-use (b = -0.19, p < 0.05) and more walking hazards (b = -0.26, p < 0.05). Findings suggest that a FL is associated with perceptions of walkability. It is essential to develop disability-friendly support systems and accommodations to encourage walking in lower-income communities.

Clinical spectrum of high-titre GAD65 antibodies.

OBJECTIVE: To determine clinical manifestations, immunotherapy responsiveness and outcomes of glutamic acid decarboxylase-65 (GAD65) neurological autoimmunity. METHODS: We identified 323 Mayo Clinic patients with high-titre (>20 nmol/L in serum) GAD65 antibodies out of 380 514 submitted anti-GAD65 samples (2003-2018). Patients classified as having GAD65 neurological autoimmunity after chart review were analysed to determine disease manifestations, immunotherapy responsiveness and predictors of poor outcome (modified Rankin score >2). RESULTS: On review, 108 patients were classified as not having GAD65 neurological autoimmunity and 3 patients had no more likely alternative diagnoses but atypical presentations (hyperkinetic movement disorders). Of remaining 212 patients with GAD65 neurological autoimmunity, median age at symptom onset was 46 years (range: 5-83 years); 163/212 (77%) were female. Stiff-person spectrum disorders (SPSD) (N=71), cerebellar ataxia (N=55), epilepsy (N=35) and limbic encephalitis (N=7) could occur either in isolation or as part of an overlap syndrome (N=44), and were designated core manifestations. Cognitive impairment (N=38), myelopathy (N=23) and brainstem dysfunction (N=22) were only reported as co-occurring phenomena, and were designated secondary manifestations. Sustained response to immunotherapy ranged from 5/20 (25%) in epilepsy to 32/44 (73%) in SPSD (p=0.002). Complete immunotherapy response occurred in 2/142 (1%). Cerebellar ataxia and serum GAD65 antibody titre >500 nmol/L predicted poor outcome. INTERPRETATION: High-titre GAD65 antibodies were suggestive of, but not pathognomonic for GAD65 neurological autoimmunity, which has discrete core and secondary manifestations. SPSD was most likely to respond to immunotherapy, while epilepsy was least immunotherapy responsive. Complete immunotherapy response was rare. Serum GAD65 antibody titre >500 nmol/L and cerebellar ataxia predicted poor outcome.

Paraneoplastic Myeloneuropathies: Clinical, Oncologic, and Serologic Accompaniments.

OBJECTIVE: To test the hypothesis that myeloneuropathy is a presenting phenotype of paraneoplastic neurologic syndromes we retrospectively reviewed clinical, radiologic, and serologic features of 32 patients with concomitant paraneoplastic spinal cord and peripheral nervous system involvement. METHODS: Observational study investigating patients with myeloneuropathy and underlying cancer or onconeural antibody seropositivity. RESULTS: Among 32 patients with paraneoplastic myeloneuropathy, 20 (63%) were women with median age 61 years (range 27-84 years). Twenty-six patients (81%) had classified onconeural antibodies (amphiphysin, n = 8; antineuronal nuclear antibody [ANNA] type 1 [anti-Hu], n = 5; collapsin response mediator protein 5 [CRMP5] [anti-CV2], n = 6; Purkinje cell cytoplasmic antibody type 1 [PCA1] [anti-Yo], n = 1; Purkinje cell cytoplasmic antibody type 2 [PCA2], n = 2; kelch-like protein 11 [KLHL11], n = 1; and combinations thereof: ANNA1/CRMP5, n = 1; ANNA1/amphiphysin, n = 1; ANNA3/CRMP5, n = 1). Cancer was confirmed in 25 cases (onconeural antibodies, n = 19; unclassified antibodies, n = 3; no antibodies, n = 3). Paraneoplastic myeloneuropathies had asymmetric paresthesias (84%), neuropathic pain (78%), subacute onset (72%), sensory ataxia (69%), bladder dysfunction (69%), and unintentional weight loss >15 pounds (63%). Neurologic examination demonstrated concomitant distal or asymmetric hyporeflexia and hyperreflexia (81%), impaired vibration and proprioception (69%), Babinski response (68%), and asymmetric weakness (66%). MRI showed longitudinally extensive (45%), tract-specific spinal cord T2 hyperintensities (39%) and lumbar nerve root enhancement (38%). Ten of 28 (36%) were unable to ambulate independently at last follow-up (median 24 months, range 5-133 months). Combined oncologic and immunologic therapy had more favorable modified Rankin Scale scores at post-treatment follow-up compared to those receiving either oncologic or immunologic therapy alone (2 [range 1-4] vs 4 [range 2-6], p < 0.001). CONCLUSIONS: Paraneoplastic etiologies should be considered in the evaluation of subacute myeloneuropathies. Recognition of key characteristics of paraneoplastic myeloneuropathy may facilitate early tumor diagnosis and initiation of immunosuppressive treatment.

Modeling esophageal protection from radiofrequency ablation via a cooling device: an analysis of the effects of ablation power and heart wall dimensions.

BACKGROUND: Esophageal thermal injury can occur after radiofrequency (RF) ablation in the left atrium to treat atrial fibrillation. Existing methods to prevent esophageal injury have various limitations in deployment and uncertainty in efficacy. A new esophageal heat transfer device currently available for whole-body cooling or warming may offer an additional option to prevent esophageal injury. We sought to develop a mathematical model of this process to guide further studies and clinical investigations and compare results to real-world clinical data. RESULTS: The model predicts that the esophageal cooling device, even with body-temperature water flow (37 °C) provides a reduction in esophageal thermal injury compared to the case of the non-protected esophagus, with a non-linear direct relationship between lesion depth and the cooling water temperature. Ablation power and cooling water temperature have a significant influence on the peak temperature and the esophageal lesion depth, but even at high RF power up to 50 W, over durations up to 20 s, the cooling device can reduce thermal impact on the esophagus. The model concurs with recent clinical data showing an 83% reduction in transmural thermal injury when using typical operating parameters. CONCLUSIONS: An esophageal cooling device appears effective for esophageal protection during atrial fibrillation, with model output supporting clinical data. Analysis of the impact of ablation power and heart wall dimensions suggests that cooling water temperature can be adjusted for specific ablation parameters to assure the desired myocardial tissue ablation while keeping the esophagus protected.

Cleveland Clinic Foundation Internal Medicine Residency Program.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians, Inc. (ACP), and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes an initiative of the Cleveland Clinic's internal medicine residents to improve diabetes care and outcomes within an underserved patient population at an East Cleveland, OH, health center.