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The transducin β-like-1 X-linked-receptor-1 gene (TBL1XR1) encodes for the TBL1XR1 protein which is involved in transcription. Single-nucleotide variants (SNVs) in the TBL1XR1 gene have been reported to be associated with Pierpont's syndrome (PS) which exhibits numerous features including global developmental delay (GDD), intellectual disability (ID), varying neurobehavioral and psychiatric manifestations with/without autism spectrum disorder (ASD), abnormal fat distribution in the distal extremities, short stature (SS), head circumference abnormalities, hearing loss (HL), and facial dysmorphisms. Eight PS patients, having a de novo mutation resulting in p.Tyr446Cys, showed no manifestations of ASD. The three other PS patients, having mutations resulting in p.Tyr446His, p.Cys325Tyr and p.Gly237Asp, respectively, and without the p.Tyr446Cys alteration, were in addition associated with neurobehavioral abnormalities, including ASD, hyperactivity, and self-mutilation tendencies. Here, via trio whole exome sequencing, we describe a 12th PS patient, the first from the Indian subcontinent, reflecting a novel TBL1XR1 p.His348Arg alteration. The proband is a 4.5-year-old male having GDD, speech delay, facial dysmorphisms, abnormal digital fat pads, hypotonia, microcephaly, patent ductus arteriosus, and ASD features. Our report strengthens the hypothesis that TBL1XR1 variants coding for the TBL1XR1 protein other than p.Tyr446Cys might be more commonly associated with a neurobehavioral phenotype and autistic tendencies.

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.

ObjectiveTo 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.MethodsObservational study investigating patients with myeloneuropathy and underlying cancer or onconeural antibody seropositivity.ResultsAmong 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).ConclusionsParaneoplastic 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.

Background: Increasing data suggest that elevated body temperature may be helpful in resolving a variety of diseases, including sepsis, acute respiratory distress syndrome (ARDS), and viral illnesses. SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), may be more temperature sensitive than other coronaviruses, particularly with respect to the binding affinity of its viral entry via the ACE2 receptor. A mechanical provision of elevated temperature focused in a body region of high viral activity in patients undergoing mechanical ventilation may offer a therapeutic option that avoids arrhythmias seen with some pharmaceutical treatments. We investigated the potential to actively provide core warming to the lungs of patients with a commercially available heat transfer device via mathematical modeling, and examine the influence of blood perfusion on temperature using this approach. Methods: Using the software Comsol Multiphysics, we modeled and simulated heat transfer in the body from an intraesophageal warming device, taking into account the airflow from patient ventilation. The simulation was focused on heat transfer and warming of the lungs and performed on a simplified geometry of an adult human body and airway from the pharynx to the lungs. Results: The simulations were run over a range of values for blood perfusion rate, which was a parameter expected to have high influence in overall heat transfer, since the heat capacity and density remain almost constant. The simulation results show a temperature distribution which agrees with the expected clinical experience, with the skin surface at a lower temperature than the rest of the body due to convective cooling in a typical hospital environment. The highest temperature in this case is the device warming water temperature, and that heat diffuses by conduction to the nearby tissues, including the air flowing in the airways. At the range of blood perfusion investigated, maximum lung temperature ranged from 37.6°C to 38.6°C. Conclusions: The provision of core warming via commercially available technology currently utilized in the intensive care unit, emergency department, and operating room can increase regional temperature of lung tissue and airway passages. This warming may offer an innovative approach to treating infectious diseases from viral illnesses such as COVID-19, while avoiding the arrhythmogenic complications of currently used pharmaceutical treatments.

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 and variable kin structure. Groups in such mixed-kin societies often comprise residents and immigrants of the same sex that compete for breeding opportunities. To understand how such mixed-kin societies form despite their potential for social conflict, we investigated the environmental causes and subsequent fitness consequences of dispersal decisions in male cooperatively breeding superb starlings (Lamprotornis superbus) that live in a climatically unpredictable environment. We show that the two alternative reproductive tactics—natal dispersal or philopatry—exhibit reproductive tradeoffs resulting in equal lifetime inclusive fitness. The tactic an individual adopts is governed by the environment its parents experience prior to laying rather than the environment it experiences during its juvenile stage. When individuals adopt the tactic not predicted by early life environmental conditions, their fitness is reduced. Ultimately, climate-driven oscillating selection may help stabilize mixed-kin animal societies, despite their reduced kin structure and potential for social conflict.

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.

ObjectivesPopulation-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.MethodsWe 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]).ResultsThere 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.DiscussionPNSs 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.

Objectives This study aimed to evaluate the effectiveness and safety of transvenous lead extraction (TLE) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Background ARVC is an increasingly diagnosed cardiomyopathy that often requires device implantation to prevent sudden death. Little is known about TLE in this setting, which has potential challenges and risks, primarily due to right ventricular (RV) wall thinning and fragility. Methods All consecutive patients with ARVC who underwent TLE at our institution between 1996 and 2016 were included. When extraction tools were used, sheaths were advanced to the RV with countertraction at the lead tip. Success and complications were defined in concordance with Heart Rhythm Society guidelines. Results Twenty-two TLE procedures in patients with ARVC involved extraction of 27 leads (22 defibrillators and 5 pacemakers). TLEs were performed due to evidence of lead malfunction (n = 17; 77%) or device infection (n = 5; 23%). Twenty-four leads (89%) were RV, and 3 leads (11%) were right atrial. The median age of the oldest extracted lead was 1,691 days (interquartile range [IQR]: 1,168 to 2,726 days). Specialized extraction tools were required in 20 procedures (91%). None required the use of a snare or a femoral workstation. The median procedural and fluoroscopic times were 152 min (IQR: 129 to 185 min) and 11 min (IQR: 6 to 18 min), respectively. Complete procedural success with removal of all leads was achieved in all cases. There were no major complications. Conclusions In a high-volume center, TLE in patients with ARVC was associated with a high success rate and a low rate of complications when guideline-established techniques and tools were used.

Objectives This study sought to assess the incidence and outcomes of life-threatening complications from atrial fibrillation ablations in a high volume center. Background With increasing rates of atrial fibrillation ablation procedures, an increase in life-threatening procedure-related complications has been reported despite improvements in technology and ablation strategies. Methods Between 2000 and 2015, 10,378 patients underwent atrial fibrillation ablation at our institution and were enrolled in a prospectively maintained data registry. We identified all patients who had life-threatening cardiac, neurological, respiratory, or vascular complications to the ablation resulting in death or requiring emergent intervention. Results Major life-threatening complications occurred in 100 patients (0.9%). The most common was pericardial effusion requiring pericardiocentesis (0.5%), with 7 (0.07%) requiring emergent surgical repair for cardiac perforation. Stroke occurred in 27 patients (0.3%) with a vast majority having an ischemic stroke (93%) followed by hemorrhagic (3.5%) and ischemic stroke with hemorrhagic conversion (3.5%). The yearly incidence of stroke decreased from an average of 1.1% per year in the first tertile (2000 to 2004) to 0.2% per year in the last 2 tertiles (2005 to 2015). Permanent neurological deficits occurred in 23 patients. Vascular complications causing hemorrhagic shock occurred in 7 patients (0.06%), 5 of whom required urgent surgical intervention. Acute coronary syndrome requiring urgent percutaneous coronary revascularization occurred in 2 patients whereas 1 developed a right coronary artery air embolus. No procedural death or atrio-esophageal fistulae occurred. Conclusions In a large quaternary care center, the incidence of life-threatening complications is low. Experienced operators, high volume, continuous quality improvement initiatives, and efficient back-up support have allowed exemplary safety profiles and 0 procedure-related deaths over 16 years.

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.

A 49-year-old woman with no relevant medical history presented to an external neurology clinic with progressive hand and foot paresthesia and gait instability for over 6 months. Initially, she reported tingling and shooting electrical-type sensations involving her feet. Within several weeks of the onset of paresthesia, she noted a burning pain sensation involving the left hand. Sensory symptoms continued to worsen and she felt pressure-like sensation around the neck and scalp region. This was shortly followed by right hand numbness and loss of dexterity. Over the next month, she developed progressive gait imbalance and transitioned to a cane for ambulation.

Background: Identifying the factors to improve the quality of life (QOL) is vital to decrease morbidity and mortality rates among older adults. Although unfavorable neighborhood features have a significant negative impact on QOL, few studies have investigated these relationships in a deprived community. The purpose of the study was to understand how neighborhood walkability is associated with QOL using the SF-36 among urban-dwelling older adults. Methods: This is a cross-sectional survey. Participants were recruited in 2018 and 2019 at regional health clinics in Flint, MI. To be eligible, participants had to be over 65 years old and Flint residents. Results: Of the 132 participants, the majority were female (66%), African American (77%), single, divorced, or widowed (75%), and educated below GED level (84%). After adjusting for gender, assistive device use, medication, and the Supplemental Security Income receipt, multiple regression analysis revealed that those with better perceptions of land-mixed use and accessibility within their neighborhood were more likely to have better physical health (β = .36, p

Insufficient physical activity (PA) is considered an independent risk factor for chronic diseases. Although older adults living in lower-income areas often experience obstacles to walking locally, few studies have compared their walking experiences and the degree of readiness to change on engaging in PA. The purpose of this study was to compare perceptions of neighborhood walkability by the stages of change among older adults living in a lower-income community. Participants were recruited in 2018 at a regional health clinic in Flint, MI. To be eligible, participants had to be over 65 years old and Flint residents. Of the 132 participants, the mean age was 69.74 (SD=5.00) years old. The majority of respondents were female (66%); African American (77%); single, divorced, or widowed (75%); and educated below a GED level (84%). The results showed that older adults at the pre-contemplation/contemplation stage (PC/C) were less likely to perceive the availability of sidewalks on most streets and more likely to complain about much traffic along the street than those at the action/maintenance stage (A/M) (p < 0.05). After controlling for covariates, multiple regression analysis showed that those at PC/C were less likely to state that their neighborhoods were accessible (β = .17*) and to perceive the presence of walking hazard (e.g., lack of sidewalks) (β = -.17*). Those who engaged in PA less than 30 minutes per day perceived the neighborhoods were accessible (β = .23*). Findings suggest that it is essential to develop friendly support systems and accommodations to encourage walking in lower-income communities.

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.

ObjectiveTo determine clinical manifestations, immunotherapy responsiveness and outcomes of glutamic acid decarboxylase-65 (GAD65) neurological autoimmunity.MethodsWe 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).ResultsOn 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.InterpretationHigh-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.

Background Ablation of the left atrium with radiofrequency (RF) energy is associated with some risks to the esophagus. Cooling the esophagus has been used as one approach to reducing esophageal injury, most commonly with direct instillation of cold liquid via gastric tube placed in the esophagus. A new esophageal cooling device avoids the risks of free liquid instillation by using a closed-loop system, and avoids the need for frequent repositioning or stopping of the procedure often required when utilizing luminal esophageal temperature (LET) monitoring. This in turn may reduce fluoroscopy requirements for the procedure. Purpose Measure the difference in fluoroscopy time required during RF ablation using an esophageal cooling device protocol, and compare this to standard LET monitoring using single or multi-sensor temperature probes. Methods We obtained total fluoroscopy time per patient from records of RF ablation procedures performed by a two operators over a 12 month period. We compared fluoroscopy times between patients treated with an esophageal cooling device to control patients who were treated with LET monitoring using either single-sensor or multi-sensor temperature probes. Results Fluoroscopy times were available for a total of 179 patients treated with an esophageal cooling device, and 118 patients treated with LET monitoring over the 12 month study period. Mean fluoroscopy time for patients treated with esophageal cooling was 4.0 minutes (SD 4.9 minutes) with a median of 2.0 minutes (IQR 1.3 to 3.8 minutes). Mean fluoroscopy time for patients undergoing LET monitoring was 5.5 minutes (SD 5.7 minutes) with a median of 3.0 minutes (IQR 1.9 to 8.4 minutes). This difference represents a 27% reduction in mean fluoroscopy time, and a 33% reduction in median fluoroscopy time in the esophageal cooling group (p Conclusions Fluoroscopy requirements were reduced by 27% with an esophageal cooling device when compared to standard LET monitoring.

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.

Fluorescein videoangiography is often used to visualize diabetic retinopathy (DR), a degenerative disease characterized by degradation of retinal blood vessels. However, more sensitive and quantitative measures of increased vessel permeability in the asymptomatic phase of DR (non-proliferative DR) could help identify patients who would benefit from therapeutic intervention to avoid vision loss. Here, a modified “adiabatic approximation to the tissue-homogeneity model” was shown in simulations and rat experiments to estimate extraction fraction within a 20%-error for physiological ranges of vascular permeability expected in nonproliferative DR, even in low-dynamic-range (8-bit) fluorescein imaging systems that are standard in many institutes.

A 20-year-old man presented with vertigo followed by hourly episodes of dysarthria and incoordination lasting 5–20 seconds (video 1). Neurologic examination was normal between episodes. The only brain/spine MRI lesion was in the right superior cerebellar peduncle (figure, A). CSF analysis revealed elevated white blood cells (6/μL [normal, 0–5]) and oligoclonal bands (≥4). Paroxysmal dysarthria–ataxia associated with CNS demyelination was diagnosed and episodes resolved with oral acetazolamide 250 mg twice daily. Subsequent MRI of the brain and spine (figure, B) confirmed multiple sclerosis. Paroxysmal dysarthria–ataxia arises from ephaptic transmission within midbrain or cerebellar multiple sclerosis lesions and may respond to carbamazepine or acetazolamide.1 It should be distinguished from genetic or contactin-associated protein-like-2 (CASPR2) immunoglobulin G–associated episodic ataxia.2

Introduction Recent clinical data show that high-power, short-duration (HPSD) radiofrequency (RF) ablation can result in a similar esophageal injury rate as traditional low-power, long-duration (LPLD) ablation. Existing methods to prevent esophageal injury have yielded mixed results and can result in prolonged procedure time, potentially increasing the incidence of post-operative cognitive dysfunction. A new esophageal cooling device currently available for whole-body temperature modulation is being studied for the prevention of esophageal injury during LPLD RF ablation and cryoablation. We sought to develop a mathematical model of HPSD ablation in order to quantify the capability of this new esophageal cooling device to protect from esophageal injury under high-power conditions. Methods Using a model we developed of HPSD RF ablation in the left atrium, we measured the change in esophageal lesion formation and the depth of lesions (measured as percent transmurality) with the esophageal cooling device in place and operating at a temperature from 5°C to 37°C. Tissue parameters, including thermal conductivity, were set to average values obtained from existing literature, and energy settings were evaluated at 50W for between 5 and 10 seconds, and at 90W for a duration of 4 seconds. Results Esophageal injury as measured by percent transmurality was considerably higher at 50W and 10s duration than at 90W of power with 4s duration, although both settings showed potential for esophageal injury. The protective effect of the esophageal cooling device was evident for both cases, with a greater effect when using 50W for 10s (Figure 1). At the coldest device settings, using a 5 min pre-cooling period also reduced the transmurality of the intended atrial lesions. Esophageal protection in HPSD ablation Conclusions Esophageal cooling with a new patient temperature management device shows protective effects against thermal injury during RF ablation across a range of tissue thermal conductivity, using a variety of high-power settings, including 90W applied for 4 seconds. Adjusting the cooling power by adjusting the circulating water temperature in the device allows for a tailoring of the protective effects to operating conditions. Acknowledgement/Funding Attune Medical

Background We sought to study longer term survival in patients with aortic stenosis ( AS ) and nondialysis chronic kidney disease ( CKD ). Methods and Results We studied 839 patients (aged 78±9 years and 51% male) with CKD and AS on echocardiogram from 2005 to 2012. Longer term all‐cause and cardiovascular mortality was compared with a CKD group without AS , propensity matched for age, sex, race, left ventricular ejection fraction and CKD stage. Cox models were used to evaluate all‐cause mortality and competing‐risks regression models censored at time of aortic valve replacement to evaluate cardiac mortality in patients with AS and CKD . Overall, 511 (61%), 252 (30%), and 76 (9%) patients had CKD stages 3a, 3b, and 4, respectively; 93% had hypertension, 28% had diabetes mellitus, and 37% had coronary artery disease. In total, 185 (22%) had mild AS, 355 (42%) had moderate AS, and 299 (36%) had severe AS (66 symptomatic). Patients with CKD and AS had higher cardiac and all‐cause mortality compared with controls with CKD and no AS ( P AS and CKD , there were 156 (19%) aortic valve replacements and 454 (54%) deaths (203 cardiac deaths) at 4.0±2.3 years of follow‐up. Lower estimated glomerular filtration rate (hazard ratio per 10 mL/min per 1.73 m 2 : 1.18; 95% CI, 1.08–1.29) was associated with increased risk of all‐cause mortality but not cardiac mortality (hazard ratio: 1.12; 95% CI, 0.97–1.30; P =0.13). Of patients undergoing aortic valve replacement, 61% had improvement in estimated glomerular filtration rate within 1 year (median percentage change=+2.8% per month). Conclusions Among patients with nondialysis CKD , AS is associated with significantly higher cardiac and all‐cause mortality; lower estimated glomerular filtration rate is associated with increased mortality, and aortic valve replacement was associated with improved survival.

Background Rifampin is recommended as adjunctive treatment for staphylococcal prosthetic valve endocarditis (PVE). It is unclear whether this should hold for surgically treated patients. The purpose of this study was to examine whether adjunctive rifampin treatment in addition to cell wall active antimicrobial agents in patients with surgically treated staphylococcal infective endocarditis (IE) results in better outcomes. Methods Patients operated on for staphylococcal IE from April 1, 2008, to July 1, 2014, were identified from our institution's IE registry. Rifampin treatment was defined as 3 or more days of rifampin postoperatively. Cox proportional hazards regression was used to compare a composite outcome of death or reoperation for IE relapse, between patients treated and not treated with rifampin, adjusted for propensity to be treated with rifampin, methicillin resistance, all-purpose refined diagnosis related group (APR-DRG) severity score, and APR-DRG mortality risk. Results In all, 273 patients were identified. The mean age was 56 years, 66% were male, 50% had PVE, 60% had S. aureus or S. lugdunensis infection, 89% had left side involvement, and 57% had invasive disease. Fifty-one (27%) received 3 or more days of rifampin postoperatively. Ninety-two patients died or underwent reoperation for IE relapse at a median of 205 days (interquartile range 56 to 718 days). In a multivariable model, patients treated with rifampin had a similar hazard of death or reoperation for IE relapse as those not treated (hazard ratio 0.76, 95% confidence interval 0.44 to 1.32, p value 0.34). The results were robust to varying definitions of rifampin treatment. Conclusions Among patients with surgically treated staphylococcal IE there was insufficient evidence to claim a reoperation-free survival benefit from treatment with rifampin. Rifampin should not be used as adjunctive therapy for staphylococcal IE in patients who have undergone surgical procedures for its treatment.

Background GFAP (glial fibrillary acidic protein)-IgG is predominantly associated with meningoencephalomyelitis, and neuropathy presentations are rare. Methods We reviewed clinical, electrodiagnostic and histopathological presentations of GFAP-IgG associated peripheral neuropathy. Results We identified six cases, five of whom had peripheral neuropathy as the initial presentation. Acute/subacute polyradicluoneuropathy or proximal nerve involvement was a common presentation. Three had demyelinating neuropathies on electrophysiological studies. Nerve biopsies (n = 2) demonstrated T-cell predominant perivascular inflammatory collections, and all patients with clinical follow up responded favorably to immunotherapy. Conclusion GFAP neuropathy represents a potentially treatable immune-mediated neuropathy and can occur with or without co-existing meningoencephalomyelitis.

Bicuspid aortic valve, one of the most common congenital cardiac malformations, is associated with other valvular abnormalities and aortopathies. It increases the risk of thoracic aortic aneurysm and dissection, infective endocarditis, and sudden cardiac death. Patients require regular surveillance for progressive valvular disease and aortopathy. Although bicuspid aortic valve may occur sporadically, many cases are inherited, so first-degree relatives should be evaluated and genetic counseling considered.

This study sought to assess the incidence and outcomes of life-threatening complications from atrial fibrillation ablations in a high volume center.With increasing rates of atrial fibrillation ablation procedures, an increase in life-threatening procedure-related complications has been reported despite improvements in technology and ablation strategies.Between 2000 and 2015, 10,378 patients underwent atrial fibrillation ablation at our institution and were enrolled in a prospectively maintained data registry. We identified all patients who had life-threatening cardiac, neurological, respiratory, or vascular complications to the ablation resulting in death or requiring emergent intervention.Major life-threatening complications occurred in 100 patients (0.9%). The most common was pericardial effusion requiring pericardiocentesis (0.5%), with 7 (0.07%) requiring emergent surgical repair for cardiac perforation. Stroke occurred in 27 patients (0.3%) with a vast majority having an ischemic stroke (93%) followed by hemorrhagic (3.5%) and ischemic stroke with hemorrhagic conversion (3.5%). The yearly incidence of stroke decreased from an average of 1.1% per year in the first tertile (2000 to 2004) to 0.2% per year in the last 2 tertiles (2005 to 2015). Permanent neurological deficits occurred in 23 patients. Vascular complications causing hemorrhagic shock occurred in 7 patients (0.06%), 5 of whom required urgent surgical intervention. Acute coronary syndrome requiring urgent percutaneous coronary revascularization occurred in 2 patients whereas 1 developed a right coronary artery air embolus. No procedural death or atrio-esophageal fistulae occurred.In a large quaternary care center, the incidence of life-threatening complications is low. Experienced operators, high volume, continuous quality improvement initiatives, and efficient back-up support have allowed exemplary safety profiles and 0 procedure-related deaths over 16 years.

Background Paravalvular leak (PVL) is often seen after aortic (AV) and mitral valve (MV) surgery, either due to infection or valve dehiscence. We sought to describe predictors of longer-term outcomes in patients who developed PVL after AV and MV surgery and were considered eligible for reoperative cardiac surgery (RCS). Methods We studied 495 such patients (65 ± 14 years, 65% men, 47% with MV PVL) who presented at our center between January 2003 and December 2011. Patients with severe mitral/aortic stenosis, patients with less than mild PVL, and those with prohibitive risk precluding RCS were excluded. Society of Thoracic Surgeons (STS) score was calculated. Primary endpoint was mortality. Results At baseline, mean STS score and left ventricular ejection fraction were 5.8 ± 4% and 52 ± 12%, respectively. In total, 105 (21%) had infective PVL and 72% had moderate or greater PVL. At a median of 8 days, 351 (71%) patients underwent RCS to repair PVL (3% in-hospital postoperative mortality), and at 6.6 ± 4 years, 230 (47%) patients died. On multivariable Cox survival analysis, greater STS score (hazard ratio or HR 1.35), mitral versus aortic PVL (HR 1.66), infectious etiology (HR 2.05), and greater right ventricular systolic pressure (HR 1.09) were associated with greater longer-term mortality, whereas surgery (HR 0.58) was associated with improved longer-term survival (all P Conclusions Patients who develop mild or greater PVL after AV/MV surgery have a high rate of longer-term mortality, despite excellent perioperative outcomes. Greater STS score, right ventricular systolic pressure, infectious etiology, and MV (vs AV) involvement were all independently associated with long-term mortality, whereas RCS for PVL closure was associated with improved longer-term survival.

Background: Atrial fibrillation recurrence after initial long-term success of catheter ablation has been described, yet not well studied. We assessed the electrophysiological findings and outcomes of repeat ablation procedures in this setting. Methods and Results: Between 2000 and 2015, 10 378 patients underwent atrial fibrillation ablation and were enrolled in a prospectively maintained data registry. From this registry, we included all 137 consecutive patients who had initial long-term success, defined as freedom from recurrent arrhythmia for >36 months off antiarrhythmics, then underwent repeat ablation for recurrent atrial fibrillation. The median arrhythmia-free period that defined long-term success was 52 months (41–68 months). In redo ablations, reconnection along at least one of the pulmonary veins (PVs) was found in 111 (81%) patients. Reconnection along a left superior, left inferior, right superior, and right inferior PV was found in 64%, 62%, 50%, and 54% of patients, respectively, and were reisolated. Additional non-PV ablations were performed in 127 (92.7%) patients: posterior wall (46%), septal to right PVs (49%), superior vena cava (35%), roof lines (52%), and cavotricuspid isthmus (33%). After a median follow-up of 17 months (5–36.9 months), 103 patients (75%) were arrhythmia free (79 off antiarrhythmics, 24 on antiarrhythmics). Conclusions: PV reconnection is the most common electrophysiological finding in patients with atrial fibrillation recurrence after long-term success, but with lower rates than what had been reported for early recurrences. In our experience, repeat ablations in this setting involve complex ablation approaches to reisolate the PVs and modify the atrial substrate and are associated with good success rates.

The built environment is commonly cited as a facilitator to local walking. Although health promotion programs targeting physical activity are available, few studies have investigated the associations of the perceived neighborhoods with the incidence of falls in the minority communities. Hence, the purpose of this preliminary study was to understand whether the perceived built environment influenced the fall experiences in older adults living in the underserved community. The preliminary cross-sectional survey was conducted at the regional health clinic in Flint, MI. Descriptive statistics and analysis of variance (ANOVA) were performed using SAS v8.4. The eligibility criteria included over 65 years old and Flint residents. Of 132 participants, the mean age was 69.75 (SD=5.00). The majority were female (68%), African Americans (80%), single, divorced or widowed (80%), and > GED (84%). The ANOVAs supported that “had fallen in the past year” was associated with “stores are within easy walking distance,” “easy to walk to a transit stop” and “there is a dirt strip that separates the streets from the sidewalks.” The fall experience was more likely to associate with the sedentary lifestyle and the comorbidities such as diabetes, fatigues, muscle spasms, and chronic pain. To summarize, the built environment increased the incidence of falls in the past year. Those who had fallen had poor health conditions. Further studies are needed for older adults to engage in physical activity. It is essential to develop the age-friendly support systems and accommodations to local walking in this community.

Functional mitral regurgitation (MR) is associated with poor outcomes and often present in non-ischemic cardiomyopathy (NICM) patients. Prior studies have demonstrated the utility of cardiac magnetic resonance (CMR) imaging in patients with NICM. However, it is unclear if CMR can also identify

Background— With improved survival of patients undergoing primary bioprosthetic aortic valve replacement (AVR), reoperation to relieve severe prosthetic aortic stenosis (PAS) is increasing. Timing of redo surgery in asymptomatic/minimally symptomatic patients remains controversial. Left ventricular (LV) global longitudinal strain (GLS) is a marker of subclinical LV dysfunction. In asymptomatic/minimally symptomatic patients with severe PAS undergoing redo AVR, we sought to determine whether LV-GLS provides incremental prognostic use. Methods and Results— We studied 191 patients with severe bioprosthetic PAS (63±16 years, 58% men) who underwent redo AVR between 2000 and 2012 (excluding mechanical PAS, severe other valve disease transcatheter AVR, and LV ejection fraction 2 , mean aortic valve gradient ≥40 mm Hg, and dimensionless index 2+ aortic regurgitation. Median LV-GLS was −14.2% (−11.4, −17.1%). At 4.2±3 years, 41 (22%) patients met the composite end point (2.5% deaths and 1% strokes at 30 days postoperatively). On multivariable Cox survival analysis, LV-GLS was independently associated with longer-term composite events (hazard ratio, 1.21; 95% confidence interval, 1.10–1.33), P P P Conclusions— In asymptomatic/minimally symptomatic patients with severe bioprosthetic PAS undergoing redo AVR, baseline LV-GLS provides incremental prognostic use over established predictors and could potentially aid in surgical timing and risk stratification.