White, Launia J.

Background: Survey studies have found an increased prevalence of migraine in patients with inflammatory bowel disease (IBD). However, the clinical characteristics of migraines in this population are unknown. We conducted a retrospective medical record review study to characterize migraines in the IBD population. Methods: Six hundred seventy-five migraine patients (280 with IBD, 395 without IBD) who were evaluated at Mayo Clinic Rochester, Mayo Clinic Arizona, or Mayo Clinic Florida between July 2009 and March 2021 were included. Patients with ICD codes for migraine and either Crohn’s disease (CD) or ulcerative colitis (UC) were selected. Electronic health care records were reviewed. Patients confirmed to have IBD and migraine were included. Demographic, IBD, and migraine characteristics were collected. Statistical analysis was completed using SAS. Results: Patients with IBD were less often male (8.6% vs 21.3%, P < .001) and had a higher Charlson Comorbidity Index (>2: 24.6% vs 15.7%, P = .003); 54.6% had CD and 39.3% had UC. Patients with IBD had migraine with aura and without aura more frequently ( OR 2.20, P < .001 and OR 2.79, P < .001, respectively) than non-IBD patients. Additionally, those with IBD less commonly had chronic migraine (OR 0.23, P < .001) and less commonly had chronic migraine or treatment for migraine (ORs 0.23-0.55, P ≤ .002). Conclusions: Migraine with and without aura have increased prevalence in IBD patients. Further study of this topic will be helpful to clarify the prevalence of migraine, establish this population’s response to treatment, and better understand the reason(s) for a low rate of treatment.

Objective We sought to determine the prevalence and possible features associated with symptoms in adult patients diagnosed with an aberrant right subclavian artery (ARSA). Methods In this single-center retrospective study, 386 adult patients were diagnosed with ARSA on chest CT scans performed between June 2016 and April 2021. Patients were grouped by the presence of symptoms, which included dysphagia, shortness of breath, cough, and upper airway wheezing. Four cardiothoracic radiologists reviewed the chest CT scans to assess features of ARSA. Agreement and multivariable logistic regression analyses were performed to determine interobserver variability and features associated with the presence of symptoms, respectively. Results The prevalence of ARSA was 1.02% and 81.3% of patients were asymptomatic. Shortness of breath (74.6%) was the most common symptom. Interobserver agreement was acceptable with most variables having an interclass correlation coefficient or κ >0.80. A patient's height > 158 cm (OR: 2.50, P = 0.03), cross-sectional area > 60 mm2 of ARSA at the level of the esophagus (OR: 2.39, P = 0.046), and angle >108 degrees formed with the aortic arch (OR: 1.99, P = 0.03) were associated with the presence of symptoms on multivariable logistic regression. A distance increase per 1 mm between ARSA and trachea (OR: 0.85, P = 0.02) was associated with decreased odds of symptoms. Conclusions Aberrant right subclavian artery is an incidental finding in most adult patients. The cross-sectional area at the level of the esophagus, angle formed with the medial wall of the aortic arch, distance between the ARSA and the trachea, and a patient's height were features associated with the presence of symptoms.

ObjectiveRecent evidence supports a link between increased TDP‐43 burden and the presence of an APOE4 gene allele in Alzheimer's disease (AD); however, it is difficult to conclude the direct effect of APOE on TDP‐43 pathology due to the presence of mixed AD pathologies. The goal of this study is to address how APOE isoforms impact TDP‐43 pathology and related neurodegeneration in the absence of typical AD pathologies.MethodsWe overexpressed human TDP‐43 via viral transduction in humanized APOE2, APOE3, APOE4 mice, and murine Apoe‐knockout (Apoe‐KO) mice. Behavior tests were performed across ages. Animals were harvested at 11 months of age and TDP‐43 overexpression‐related neurodegeneration and gliosis were assessed. To further address the human relevance, we analyzed the association of APOE with TDP‐43 pathology in 160 postmortem brains from autopsy‐confirmed amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with motor neuron disease (FTLD‐MND) in the Mayo Clinic Brain Bank.ResultsWe found that TDP‐43 overexpression induced motor function deficits, neuronal loss, and gliosis in the motor cortex, especially in APOE2 mice, with much milder or absent effects in APOE3, APOE4, or Apoe‐KO mice. In the motor cortex of the ALS and FTLD‐MND postmortem human brains, we found that the APOE2 allele was associated with more severe TDP‐43‐positive dystrophic neurites.InterpretationOur data suggest a genotype‐specific effect of APOE on TDP‐43 proteinopathy and neurodegeneration in the absence of AD pathology, with the strongest association seen with APOE2. ANN NEUROL 2023;93:830–843

AbstractBackgroundInter‐cellular communication within the gliovascular unit (GVU) is critical for cerebral blood flow regulation, maintenance of the blood‐brain‐barrier (BBB) properties, and brain energy metabolism. Although numerous cell biology studies demonstrate the role of the GVU for BBB breakdown in Alzheimer’s disease (AD), the precise molecular changes contributing to its pathophysiology are unclear.MethodWe performed single nucleus RNA sequencing (snRNAseq) of temporal cortex tissue in 24 AD and control brains to understand the transcriptional changes in the cells of GVU. We acquired the snRNAseq profile of 79,751 total brain cells that comprise 6,541 astrocytes and 2,210 vascular cells. The latter formed three distinct vascular clusters characterized as activated pericytes, endothelia and resting pericytes. We identified differentially expressed genes (DEGs) and their enriched pathways in these clusters and detected the most transcriptional changes within activated pericytes. Using our data and a knowledge‐based predictive algorithm, we discovered and prioritized molecular interactions between vascular and astrocyte clusters, the main cell types of the GVU of the BBB.ResultsVascular targets predicted to interact with astrocytic ligands have biological functions in signalling, angiogenesis, amyloid ß metabolism and cytoskeletal structure. Top astrocytic and vascular interacting molecules include both novel and known AD risk genes such as APOE, APP and ECE1. We validated gene expression changes using qPCR. We are in the process of evaluating these gene expression changes in antemortem blood from AD and control participants.ConclusionOur findings provide valuable information into the transcriptional changes in predicted vascular‐astrocytic partners at the GVU, highlighting insights into the molecular mechanisms of BBB breakdown in AD.

Mutations in the CSF1R gene are the most common cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a neurodegenerative disease with rapid progression and ominous prognosis. Hematopoietic stem cell transplantation (HSCT) has been increasingly offered to patients with CSF1R-ALSP. However, different therapy results were observed, and it was not elucidated which patient should be referred for HSCT. This study aimed to determine predictors of good and bad HSCT outcomes in CSF1R-ALSP. We retrospectively analyzed 15 patients, 14 symptomatic and 1 asymptomatic, with CSF1R-ALSP that underwent HSCT. Median age of onset was 39 years, and the median age of HSCT was 43 years. Cognitive impairment was the most frequent initial manifestation (43%), followed by gait problems (21%) and neuropsychiatric symptoms (21%). Median post-HSCT follow-up was 26 months. Good outcomes were associated with gait problems as initial (p = 0.041) and predominant (p = 0.017) manifestation and younger age at HSCT (p = 0.044). Cognitive impairment as first manifestation was a predictor of a bad outcome (p = 0.016) and worsening of cognition post-HSCT (p = 0.025). In conclusion, gait problems indicated a milder phenotype with better response to HSCT and good therapy outcomes. In contrast, patients with a higher burden of cognitive symptoms were most likely not to benefit from HSCT.

Précis: Surgical and clinical success rates were similar among Ahmed FP7, and Baerveldt 250 and 350 glaucoma drainage devices at three years. Purpose: To compare rates of surgical and clinical success in patients with Ahmed FP7 (FP7), Baerveldt 250 (B250), or Baerveldt 350 (B350) glaucoma drainage devices (GDDs). Design: A retrospective cohort study. Methods: A total of 157 eyes of 129 adult patients with FP7, B250, B350 GDDs, and 190 eyes of 99 medically controlled glaucoma patients were enrolled at a tertiary care institution from August 2017 through July 2019. They were followed through April 2020. The main outcome measures included surgical and clinical failure. Surgical failure was defined as intraocular pressure (IOP) outside 5–21 mm Hg, IOP reduced <20% below baseline, additional glaucoma surgery, GDD removal, or no light perception. Eyes that did not meet their goal IOP ranges or required secondary glaucoma interventions were deemed clinical failures. Results: A total of 43 (12.4%) FP7, 36 (10.4%) B250, 78 (22.5%) B350, and 190 (54.8%) medically treated control eyes were enrolled. By the postoperative year 3 visit, 10 (23.2%) FP7, 11 (30.6%) B250, and 32 (41.0%) B350 eyes had met a surgical failure criterion (P=0.127). There were no significant differences in the numbers of eyes meeting their IOP target ranges (P=0.510), and rates of secondary glaucoma surgeries (P=0.270). Overall clinical success was attained among 83.3% FP7, 81.8% B250, and 68.0% B350 eyes (P=0.447). Conclusions: The GDD groups were similar in their rates of success, based on both the surgical and clinical success definitions.

Purpose To determine whether metabolic syndrome (MetS) is a risk factor for various forms of optic neuropathy including non-arteritic anterior ischaemic optic neuropathy (NAION). Methods This population-based analysis identified patients ≥40 years of age in Olmsted County, Minnesota, USA using the Rochester Epidemiology Project 2005–2018. Patients with MetS were identified if three or more of the five standard criteria for diagnosing MetS were present: systemic hypertension, hyperglycaemia, hypertriglyceridaemia, reduced high-density lipoprotein cholesterol (hypoalphalipoproteinaemia) and central adiposity defined by increased body mass index. Charts of patients identified as having an optic neuropathy were reviewed to record specific diagnoses and compared with patients without ocular pathology other than cataract. The odds ratio (OR) of association with MetS was calculated and adjusted for age, sex and race with multivariate analysis for the various optic neuropathies. Results Patients with MetS were more likely to have an optic neuropathy than those without (OR 2.2, p<0.001). After adjusting for age, sex and race, the only optic neuropathy found to be significantly associated with MetS was NAION (OR 6.17, p=0.002). For patients with NAION, though each individual component of MetS was individually significantly associated with MetS, further analysis suggested that hypertriglyceridaemia, hypoalphalipoproteinaemia and hyperglycaemia were likely the key drivers in the overall significance between NAION and MetS. Conclusion Patients with MetS were more likely to have NAION. Further studies are needed to determine whether MetS is a modifiable risk factor for NAION.

Background: Non-vitamin K antagonist oral anticoagulants (NOAC) have replaced vitamin K antagonist (VKA) oral anticoagulants as the first-line treatment option for stroke prevention in high-risk patients with atrial fibrillation. With VKA therapy, disease and treatment-related knowledge is associated with improved adherence and outcomes. There is concern that due to the lack of need for ongoing visits for laboratory monitoring in patients on NOACs, there is less opportunity for education, leading to poor disease- and treatment-related knowledge in this patient group. Methods: One hundred ninety-nine (199) patients presenting to 2 primary care clinics on NOAC therapy were surveyed regarding atrial fibrillation and their knowledge regarding NOACs. Chart review was completed to determine patient characteristics and data obtained was compared with survey results to determine the accuracy of the survey responses. Results: Patients with a lower degree of NOAC knowledge tended to be older ( P < .001), have higher Charlson Comorbidity Index scores ( P = .001), use apixaban more often ( P = .008), and have been on NOACs for a shorter time period ( P = .007). Conclusions: There is an opportunity to improve NOAC-related knowledge in patients with atrial fibrillation. When developing educational interventions, patient characteristics associated with poor knowledge should be considered. Based on our results, these are patients who are older, more medically complex, are on apixaban, and have been on NOAC therapy for a shorter duration.

AbstractBackgroundAbdominal arterial calcification (AAC) is common among candidates for kidney transplant. The aim of this study is to correlate AAC score value with post‐kidney transplant outcomes.MethodsWe modified the coronary calcium score by changing the intake data points and used it to quantitate the AAC. We conducted a retrospective clinical study of all adult patients who were transplanted at our center, between 2010 and 2013, and had abdominal computed tomography scan done before transplantation. Outcomes included mortality, pulse pressure (PP) measured by 24 h ambulatory blood pressure monitoring system, and kidney allograft function measured by iothalamate clearance.ResultsFor each 1000 increase of AAC score value, there is an associated 1.05 increase in the risk of death (95% CI 1.02, 1.08) (p < 0.001). Overall median AAC value for all patients was 1784; Kaplan–Meier curve showed reduced survival of all‐cause mortality for patients with AAC score value above median and reduced survival among patients with cardiac related mortality. The iothalamate clearance was lower among patients with total AAC score value above the median. Patients with abnormal PP (< 40 or > 60 mmHg) had an elevated median AAC score value at 4319.3 (IQR 1210.4, 11097.1) compared to patients with normal PP with AAC score value at 595.9 (IQR 9.9, 2959.9) (p < 0.001).ConclusionWe showed an association of AAC with patients’ survival and kidney allograft function after kidney transplant. The AAC score value could be used as a risk stratification when patients are considered for kidney transplant.