Faculty Bibliography

Religious experiences in epilepsy patients have provoked much interest with suggestions that hyperreligiosity is associated with temporal lobe seizures. Extreme varieties of religious behavior may be more frequent in epilepsy patients during ictal activity or during post-ictal psychotic episodes. We report a 75 year-old man with epilepsy who developed a progressive decline in cognition and behavior following a religious conversion 15 years earlier. He subsequently developed religious delusions of increasing severity and symptoms of Capgras syndrome. Brain imaging revealed bilateral posterior cortical atrophy, chronic right parieto-occipital encephalomalacia, and right mesial temporal sclerosis. Electroencephalograms and neuropsychological testing revealed initial right temporal lobe abnormalities followed by progressive frontal and bilateral dysfunction. The case highlights how a history of seizures, superimposed on sensory deprivation and a progressive impairment of right posterior and bilateral anterior brain function, may have contributed to religious conversion, which was followed by dementia and delusions involving religious content.

The utility of the Victoria Symptom Validity Test (VSVT) as a performance validity test (PVT) has been primarily established using response accuracy scores. However, the degree to which response latency may contribute to accurate classification of performance invalidity over and above accuracy scores remains understudied. Therefore, this study investigated whether combining VSVT accuracy and response latency scores would increase predictive utility beyond use of accuracy scores alone. Data from a mixed clinical sample of 163 patients, who were administered the VSVT as part of a larger neuropsychological battery, were analyzed. At least four independent criterion PVTs were used to establish validity groups (121 valid/42 invalid). Logistic regression models examining each difficulty level revealed that all VSVT measures were useful in classifying validity groups, both independently and when combined. Individual predictor classification accuracy ranged from 77.9 to 81.6%, indicating acceptable to excellent discriminability across the validity indices. The results of this study support the value of both accuracy and latency scores on the VSVT to identify performance invalidity, although the accuracy scores had superior classification statistics compared to response latency, and mean latency indices provided no unique benefit for classification accuracy beyond dimensional accuracy scores alone.

Importance/UNASSIGNED:Non-communicable chronic diseases (NCDs) such as obesity, type 2 diabetes, heart disease, and cancer were rare among non-western populations with traditional diets and lifestyles. As populations transitioned toward industrialized diets and lifestyles, NCDs developed. Objective/UNASSIGNED:We performed a systematic literature review to examine the effects of diet and lifestyle transitions on NCDs. Evidence Review/UNASSIGNED:We identified 22 populations that underwent a nutrition transition, eleven of which had sufficient data. Of these, we chose four populations with diverse geographies, diets and lifestyles who underwent a dietary and lifestyle transition and explored the relationship between dietary changes and health outcomes. We excluded populations with features overlapping with selected populations or with complicating factors such as inadequate data, subgroups, and different study methodologies over different periods. The selected populations were Yemenite Jews, Tokelauans, Tanushimaru Japanese, and Maasai. We also review transition data from seven excluded populations (Pima, Navajo, Aboriginal Australians, South African Natal Indians and Zulu speakers, Inuit, and Hadza) to assess for bias. Findings/UNASSIGNED:The three groups that replaced saturated fats (SFA) from animal (Yemenite Jews, Maasai) or plants (Tokelau) with refined carbohydrates had negative health outcomes (e.g., increased obesity, diabetes, heart disease). Yemenites reduced SFA consumption by >40% post-transition but men's BMI increased 19% and diabetes increased ~40-fold. Tokelauans reduced fat, dramatically reduced SFA, and increased sugar intake: obesity and diabetes rose. The Tanushimaruans transitioned to more fats and less carbohydrates and used more anti-hypertensive medications; stroke and breast cancer declined while heart disease was stable. The Maasai transitioned to lower fat, SFA and higher carbohydrates and had increased BMI and diabetes. Similar patterns were observed in the seven other populations. Conclusion/UNASSIGNED:The nutrient category most strongly associated with negative health outcomes - especially obesity and diabetes - was sugar (increased 600-650% in Yemenite Jews and Tokelauans) and refined carbohydrates (among Maasai, total carbohydrates increased 39% in men and 362% in women), while increased calories was less strongly associated with these disorders. Across 11 populations, NCDs were associated with increased refined carbohydrates more than increased calories, reduced activity or other factors, but cannot be attributed to SFA or total fat consumption.

OBJECTIVE/UNASSIGNED:To explore factors associated with anticoagulation (AC) initiation after atrial fibrillation (AF) diagnosis. DESIGN/UNASSIGNED:Retrospective cohort study. SETTING/UNASSIGNED:Urban medical center. PATIENTS/UNASSIGNED:Adults with emergency department (ED) diagnosis of new onset AF from 1/1/2017-1/1/2020 discharged home. METHODS/UNASSIGNED:We compared patients initiated on AC, our primary outcome, to those not initiated on AC. Stroke, major bleeding, and AC initiation within 1 year of visit were secondary outcomes. We hypothesized that minority race and non-English language preference are associated with failure to initiate AC. RESULTS/UNASSIGNED:-VASc score (3[2-4]) vs. 2[1-4]; P=.047) were associated with AC. Of 73 patients with follow-up data at 1 year, 2 (8%) not initiated on AC had strokes, 2 (4%) initiated on AC had major bleeds, and 15 (62.5%) not initiated on AC in the ED subsequently were initiated on AC. CONCLUSION/UNASSIGNED:More than half of ED patients with new AF eligible for AC were initiated on it. Work to improve AC utilization among patients with new AF who left AMA from ED and those who prefer to communicate in a non-English language may be warranted.

BACKGROUND:Tuberous sclerosis complex (TSC) and some focal cortical dysplasias (FCDs) are associated with dysfunctional mTOR signaling, resulting in increased cell growth and ribosomal S6 protein phosphorylation (phospho-S6). mTOR inhibitors can reduce TSC tumor growth and seizure frequency, and preclinical FCD studies indicate seizure suppression. This pilot study evaluated safety of mTOR inhibitor everolimus in treatment resistant (failure of >2 anti-seizure medications) TSC and FCD patients undergoing surgical resection and to assess mTOR signaling and molecular pathways. METHODS AND FINDINGS/RESULTS:We evaluated everolimus in 14 treatment resistant epilepsy patients undergoing surgical resection (4.5 mg/m2 daily for 7 days; n = 4 Active, mean age 18.3 years, range 4-26; n = 10, Control, mean age 13.1, range 3-45). Everolimus was well tolerated. Mean plasma everolimus in Active participants were in target range (12.4 ng/ml). Brain phospho-S6 was similar in Active and Control participants with a lower trend in Active participants, with Ser235/236 1.19-fold (p = 0.67) and Ser240/244 1.15-fold lower (p = 0.66). Histologically, Ser235/236 was 1.56-fold (p = 0.37) and Ser240/244 was 5.55-fold lower (p = 0.22). Brain proteomics identified 11 proteins at <15% false discovery rate associated with coagulation system (p = 1.45x10-9) and acute phase response (p = 1.23x10-6) activation. A weighted gene correlation network analysis (WGCNA) of brain proteomics and phospho-S6 identified 5 significant modules. Higher phospho-S6 correlated negatively with cellular respiration and synaptic transmission and positively with organophosphate metabolic process, nuclear mRNA catabolic process, and neuron ensheathment. Brain metabolomics identified 14 increased features in Active participants, including N-acetylaspartylglutamic acid. Plasma proteomics and cytokine analyses revealed no differences. CONCLUSIONS:Short-term everolimus before epilepsy surgery in TSC and FCD resulted in no adverse events and trending lower mTOR signaling (phospho-S6). Future studies should evaluate implications of our findings, including coagulation system activation and everolimus efficacy in FCD, in larger studies with long-term treatment to better understand molecular and clinical effects. CLINICAL TRIALS REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT02451696.

Meningiomas are the most common non-metastatic brain tumors, and although the majority are relatively slow-growing and histologically benign, a subset of meningiomas are aggressive and remain challenging to treat. Despite a standard of care that includes surgical resection and radiotherapy, and recent advances in meningioma molecular grouping, there are no systemic medical options for patients with meningiomas that are resistant to standard interventions. Misactivation of the cell cycle at the level of CDK4/6 is common in high-grade or molecularly aggressive meningiomas, and CDK4/6 has emerged as a potential target for systemic meningioma treatments. In this review, we describe the preclinical evidence for CDK4/6 inhibitors as a treatment for high-grade meningiomas and summarize evolving clinical experience with these agents. Further, we highlight upcoming clinical trials for patients meningiomas, and discuss future directions aimed at optimizing the efficacy of these therapies and selecting patients most likely to benefit from their use.

BACKGROUND:Alzheimer's disease, the most common cause of dementia, causes a progressive and irreversible deterioration of cognition that can sometimes be difficult to diagnose, leading to suboptimal patient care. METHODS:We developed a predictive model that computes multi-regional statistical morpho-functional mesoscopic traits from T1-weighted MRI scans, with or without cognitive scores. For each patient, a biomarker called "Alzheimer's Predictive Vector" (ApV) was derived using a two-stage least absolute shrinkage and selection operator (LASSO). RESULTS:is significantly altered in patients with ADrp-like phenotype. CONCLUSIONS:This new data analytic method demonstrates potential for increasing accuracy of Alzheimer diagnosis.

The inclusion of people with disabilities has historically been, and continues to be, challenging work. In the health professions, the practice of inclusion should promote and advance the dissemination of efforts to decrease the impact of societal and physical barriers on the lives of people with disability, as well as promote innovative approaches to effectively foster an inclusive society. In addition to a focus on concepts such as the intact abilities of people with disabilities and the facilitation of community participation, an important shift in inclusion-related research requires listening to the lived experience of individuals with disabilities. Listening to their lived experiences and including the valuable insights gleaned from their insider's perspective can enrich efforts to evaluate clinical and educational programs, define population needs, and set research agendas and rehabilitation goals. Building on seminal work from Tamara Dembo, Beatrice Wright, and Margaret Brown, this communication from the Disability Representation Task Force at the American Congress of Rehabilitation Medicine also explores how healthcare providers living with a disability can make a significant contribution to rehabilitation treatment by analyzing how their own experience applies to clinical practice.