“Open surgery or laser interstitial thermal therapy for low-grade epilepsy-associated tumors of the temporal lobe: A single-institution consecutive series” (2022) Epilepsy and Behavior
Open surgery or laser interstitial thermal therapy for low-grade epilepsy-associated tumors of the temporal lobe: A single-institution consecutive series(2022) Epilepsy and Behavior, 130, art. no. 108659, .
Hedaya, A.A.a , Hewitt, K.C.b , Hu, R.c , Epstein, C.M.b , Gross, R.E.a b , Drane, D.L.b d e , Willie, J.T.a b f
a Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, United Statesb Department of Neurology, Emory University School of Medicine, Atlanta, GA, United Statesc Department of Radiology, Emory University School of Medicine, Atlanta, GA, United Statesd Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, United Statese Department of Neurology, University of Washington, Seattle, WA, United Statesf Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States
AbstractOutcomes of treating low-grade epilepsy-associated tumors (LEATs) in the temporal lobe with MRI-guided laser interstitial thermal therapy (MRgLITT) remain poorly characterized. This study aimed to compare the safety and effectiveness of treating temporal lobe LEATs with MRgLITT versus open resection in a consecutive single-institution series. We reviewed all adult patients with epilepsy that underwent surgery for temporal lobe LEATs at our institution between 2002 and 2019, during which time we switched from open surgery to MRgLITT. Surgical outcome was categorized by Engel classification at >12mo follow-up and Kaplan–Meir analysis of seizure freedom. We recorded hospital length of stay, adverse events, and available neuropsychological results. Of 14 total patients, 7 underwent 9 open resections, 6 patients underwent MRgLITT alone, and 1 patient underwent an open resection followed by MRgLITT. Baseline group demographics differed and were notable for preoperative duration of epilepsy of 9.0 years (range 1–36) for open resection versus 14.0 years (range 2–34) for MRgLITT. Median length of stay was one day shorter for MRgLITT compared to open resection (p=<.0001). There were no major adverse events in the series, but there were fewer minor adverse events following MRgLITT. At 12mo follow-up, 50% (5/10) of patients undergoing open resection and 57% (4/7) of patients undergoing MRgLITT were free of disabling seizures (Engel I). When comparing patients who underwent similar procedures in the dominant temporal lobe, patients undergoing MRgLITT had fewer and milder material-specific neuropsychological declines than patients undergoing open resections. In this small series, MRgLITT was comparably safe and effective relative to open resection of temporal lobe LEATs. © 2022 Elsevier Inc.
Author KeywordsBrain tumor; Epilepsy; Laser interstitial thermal therapy; Low-grade glioma; Neurocognitive outcome; Seizure outcome
Funding detailsNational Institutes of HealthNIHNational Institute of Neurological Disorders and StrokeNINDSK02NS070960, R01NS088748
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Neutralizing antibodies protect mice against Venezuelan equine encephalitis virus aerosol challenge” (2022) The Journal of Experimental Medicine
Neutralizing antibodies protect mice against Venezuelan equine encephalitis virus aerosol challenge(2022) The Journal of Experimental Medicine, 219 (4), .
Kafai, N.M.a b , Williamson, L.E.c d , Binshtein, E.c , Sukupolvi-Petty, S.a , Gardner, C.L.e f g , Liu, J.a , Mackin, S.a b , Kim, A.S.a b , Kose, N.c , Carnahan, R.H.c h , Jung, A.b , Droit, L.b , Reed, D.S.e f , Handley, S.A.b , Klimstra, W.B.e f , Crowe, J.E.c d h , Diamond, M.S.a b i j
a Department of Medicine, Washington University School of Medicine, St. Louis, MOb Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MOc Vanderbilt Vaccine Center, Vanderbilt University Medical Center, TN, Nashville, United Statesd Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, TN, Nashville, United Statese Center for Vaccine Research, University of Pittsburgh, PA, Pittsburgh, United Statesf Department of Immunology, University of Pittsburgh, PA, Pittsburgh, United Statesg United States Army Research Institute for Infectious Diseases, MD, Fort Detrickh Department of Pediatrics, Vanderbilt University Medical Center, TN, Nashville, United Statesi Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MOj The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO
AbstractVenezuelan equine encephalitis virus (VEEV) remains a risk for epidemic emergence or use as an aerosolized bioweapon. To develop possible countermeasures, we isolated VEEV-specific neutralizing monoclonal antibodies (mAbs) from mice and a human immunized with attenuated VEEV strains. Functional assays and epitope mapping established that potently inhibitory anti-VEEV mAbs bind distinct antigenic sites in the A or B domains of the E2 glycoprotein and block multiple steps in the viral replication cycle including attachment, fusion, and egress. A 3.2-Å cryo-electron microscopy reconstruction of VEEV virus-like particles bound by a human Fab suggests that antibody engagement of the B domain may result in cross-linking of neighboring spikes to prevent conformational requirements for viral fusion. Prophylaxis or postexposure therapy with these mAbs protected mice against lethal aerosol challenge with VEEV. Our study defines functional and structural mechanisms of mAb protection and suggests that multiple antigenic determinants on VEEV can be targeted for vaccine or antibody-based therapeutic development. © 2022 Kafai et al.
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Neuronal mechanism of a BK channelopathy in absence epilepsy and dyskinesia” (2022) Proceedings of the National Academy of Sciences of the United States of America
Neuronal mechanism of a BK channelopathy in absence epilepsy and dyskinesia(2022) Proceedings of the National Academy of Sciences of the United States of America, 119 (12), pp. e2200140119.
Dong, P.a , Zhang, Y.a , Hunanyan, A.S.b , Mikati, M.A.b c , Cui, J.d , Yang, H.a c
a Department of Biochemistry, Duke University Medical Center, Durhamb Department of Pediatrics, Duke University Medical Center, Durhamc Department of Neurobiology, Duke University Medical Center, Durhamd Department of Biomedical Engineering, Washington University in Saint Louis, MO, Saint Louis 63130, Seychelles
AbstractSignificanceBK channelopathy has been increasingly implicated in diverse neurological disorders, including epilepsy and movement, cognitive, and neurodevelopmental disorders. However, precision medicine to treat BK channelopathy is lacking. We characterized a mouse model carrying a gain-of-function BK channelopathy D434G from a large family of patients with absence epilepsy and paroxysmal dyskinesia. The BK-D434G mice manifest the clinical features of absence seizures and exhibit severe locomotor defects including involuntary dyskinesia-like behavior. Pharmacological inhibition of BK channels suppresses neuronal hyperactivity and mitigates absence seizure and the locomotor defects. The BK-D434G mice thus serve as a model to understand the pathogenic mechanisms of absence epilepsy and dyskinesia. Our study also suggests that BK inhibition is a promising strategy for treating BK gain-of-function channelopathy.
Author Keywordsabsence seizure; BK channel; channelopathy; dyskinesia; epilepsy
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Association between Workplace Absenteeism and Alcohol Use Disorder from the National Survey on Drug Use and Health, 2015-2019” (2022) JAMA Network Open
Association between Workplace Absenteeism and Alcohol Use Disorder from the National Survey on Drug Use and Health, 2015-2019(2022) JAMA Network Open, 5 (3), art. no. e222954, .
Parsley, I.C.a , Dale, A.M.b , Fisher, S.L.a , Mintz, C.M.a , Hartz, S.M.a , Evanoff, B.A.b , Bierut, L.J.a
a Department of Psychiatry, Washington University, School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, United Statesb Department of Medicine, Washington University, School of Medicine, St Louis, MO, United States
AbstractImportance: Alcohol use disorder (AUD) is common and associated with increased morbidity. The degree to which AUD currently factors into workplace absenteeism needs further characterization in the US. Objective: To examine the association between AUD and workplace absenteeism in a nationally representative sample. Design, Setting, and Participants: This cross-sectional study used data from a nationally representative sample of noninstitutionalized US residents from the 2015-2019 National Survey on Drug Use and Health to examine the association of AUD with workplace absenteeism. Eligible respondents were aged 18 years and older who reported full-time employment. Data were analyzed from March to September 2021. Main Outcomes and Measures: Primary outcomes were markers of workplace absenteeism as defined by the number of days missed from work because of illness or injury and days skipped from work in the last 30 days. Descriptive statistics, prevalence ratios, and logistic regression analyses were performed to assess the association between AUD and absenteeism. Results: A total of 110701 adults aged 18 years and older reported current full-time employment (58948 [53.2%] men, 51753 [46.8%] women; 12776 [11.5%] Black, 18096 [16.3%] Hispanic, and 69506 [62.8%] White respondents). Weighted prevalence of AUD in this sample of working adults was 9.3% (95% CI, 9.0%-9.5%); 6.2% (95% CI, 6.0%-6.4%) of respondents met criteria for mild AUD, 1.9% (95% CI, 1.7%-2.0%) for moderate AUD, and 1.2% (95% CI, 1.1%-1.3%) for severe AUD. Mean days missed from work annually increased in a stepwise fashion with increasing AUD severity (no AUD, 13.0 days; 95% CI, 12.7-13.2 days; mild AUD, 17.7 days; 95% CI, 16.4-19.1 days; moderate AUD, 23.6 days; 95% CI, 21.5-25.7 days; severe AUD, 32.3 days; 95% CI, 27.5-37.0 days). People with AUD represented 9.3% of the full-time workforce and contributed to 14.1% of total reported workplace absences. Conclusions and Relevance: In this cross-sectional study, AUD was disproportionately associated with an increased prevalence of workplace absenteeism, with individuals with AUD contributing over 232 million missed workdays annually. These results provide economic incentive for increased investment in AUD prevention and treatment, both for employers and policy makers. © 2022 Parsley IC et al.
Funding detailsNational Institute of Mental HealthNIMHR25 MH112473National Institute on Drug AbuseNIDAK12 DA041449, R34 DA050044National Institute on Alcohol Abuse and AlcoholismNIAAAU10 AA008401Substance Abuse and Mental Health Services AdministrationSAMHSAH79TI082566National Institute for Occupational Safety and HealthNIOSH5U19 OH008868
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Nerve transfers for femoral nerve palsy: an updated approach and surgical technique” (2022) Journal of Neurosurgery
Nerve transfers for femoral nerve palsy: an updated approach and surgical technique(2022) Journal of Neurosurgery, 136 (3), pp. 856-866.
Peters, B.R.a , Ha, A.Y.a , Moore, A.M.b , Tung, T.H.a
a Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University, School of Medicine, St. Louis, MO, United Statesb Department of Plastic and Reconstructive Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, United States
AbstractOBJECTIVE Femoral nerve palsy results in significant impairment of lower extremity function due to the loss of quadriceps muscle function. The authors have previously described their techniques utilizing the anterior obturator and sartorius nerves for transfer in cases of femoral nerve palsy presenting within 1 year of injury. In the current study, the authors discuss their updated techniques, results, and approach to partial and complete femoral nerve palsies using femoral nerve decompression and nerve transfers. METHODS They conducted a retrospective review of patients with femoral nerve palsies treated with their technique at the Washington University School of Medicine in 2008-2019. Primary outcomes were active knee extension Medical Research Council (MRC) grades and visual analog scale (VAS) pain scores. RESULTS Fourteen patients with femoral nerve palsy were treated with femoral nerve decompression and nerve transfer: 4 with end-to-end (ETE) nerve transfers, 6 with supercharged end-to-side (SETS) transfers, and 4 with ETE and SETS transfers, using the anterior branch of the obturator nerve, the sartorius branches, or a combination of both. The median preoperative knee extension MRC grade was 2 (range 0-3). The average preoperative VAS pain score was 5.2 (range 1-9). Postoperatively, all patients attained an MRC grade 4 or greater and subjectively noted improved strength and muscle bulk and more natural gait. The average postoperative pain score was 2.3 (range 0-6), a statistically significant improvement (p = 0.001). CONCLUSIONS Until recently, few treatments were available for high femoral nerve palsy. A treatment strategy involving femoral nerve decompression and nerve transfers allows for meaningful functional recovery and pain relief in cases of partial and total femoral nerve palsy. An algorithm for the management of partial and complete femoral nerve palsies and a detailed description of surgical techniques are presented. © AANS 2022.
Author Keywordsfemoral nerve palsy; nerve decompression; nerve transfer; peripheral nerve; surgical technique
Document Type: Conference PaperPublication Stage: FinalSource: Scopus
“Externalizing personality characteristics define clinically relevant subgroups of alcohol use disorder” (2022) PLoS ONE
Externalizing personality characteristics define clinically relevant subgroups of alcohol use disorder(2022) PLoS ONE, 17 (3 March), art. no. e0265577, .
Kovács, I.a , Gál, B.I.a , Horváth, Z.b c , Demeter, I.a , Rózsa, S.d e , Janka, Z.a , Urbán, R.c , Demetrovics, Z.c f , Andó, B.a
a Department of Psychiatry, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungaryb Doctoral School of Psychology, ELTE Eötvös Loránd University, Budapest, Hungaryc Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungaryd Department of Psychiatry, Washington University, School of Medicine, St. Louis, MO, United Statese Institute of Psychology, Károli Gáspár University of the Reformed Church in Hungary, Budapest, Hungaryf Centre of Excellence in Responsible Gaming, University of Gibraltar, Gibraltar, Gibraltar
AbstractAims Higher levels of externalizing characteristics, i.e. impulsivity, novelty seeking and aggression, could contribute to the development, progression and severity of alcohol use disorder (AUD). The present study aims to explore whether these externalizing characteristics together have a potential group-forming role in AUD using latent profile analysis (LPA). Methods Externalizing characteristics of 102 AUD patients were analyzed using LPA to explore the group-forming role of externalizing symptoms; groups were compared in terms of demographic and alcohol-related variables, indices of psychopathological, depressive and anxiety symptom severity. Results LPA revealed and supported a two-group model based on externalizing symptoms. The group with higher levels of externalizing symptoms showed significantly elevated levels of alcohol-related and anxio-depressive symptoms. Conclusions Externalizing characteristics converge and have a group-forming role in chronic AUD, and are associated with a more severe form of AUD. By making the diagnostic category less heterogeneous, these different subtypes within AUD may provide aid in tailoring treatments to patients’ specific needs. © 2022 Kovács et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Analysis of X-inactivation status in a Rett syndrome natural history study cohort” (2022) Molecular Genetics and Genomic Medicine
Analysis of X-inactivation status in a Rett syndrome natural history study cohort(2022) Molecular Genetics and Genomic Medicine, .
Fang, X.a , Butler, K.M.a , Abidi, F.a , Gass, J.n o , Beisang, A.b , Feyma, T.b , Ryther, R.C.c , Standridge, S.d e , Heydemann, P.f , Jones, M.g , Haas, R.h , Lieberman, D.N.i , Marsh, E.j , Benke, T.A.k , Skinner, S.a , Neul, J.L.l , Percy, A.K.m , Friez, M.J.a , Caylor, R.C.a
a Greenwood Genetic Center, Greenwood, SC, United Statesb Gillette Children’s Specialty Healthcare, St. Paul, MN, United Statesc Department of Neurology, Washington University School of Medicine, St. Louis, MO, United Statesd Division of Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United Statese Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, United Statesf Rush University Medical Center, Chicago, IL, United Statesg Oakland Children’s Hospital, UCSF, Oakland, CA, United Statesh University of California San Diego, San Diego, CA, United Statesi Department of Neurology, Boston Children’s Hospital, Boston, MA, United Statesj Children’s Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA, United Statesk University of Colorado School of Medicine, Children’s Hospital Colorado-Aurora, Denver, CO, United Statesl Vanderbilt Kennedy Center, Vanderbilt University Medical Center, Nashville, TN, United Statesm The University of Alabama at Birmingham, Birmingham, AL, United Statesn Florida Cancer Specialists & Research Institute, Fort Myers, FL, United Stateso Florida Cancer Specialists & Research Institute, Fort Myers, FL, United States
AbstractBackground: Rett syndrome (RTT) is a rare neurodevelopmental disorder associated with pathogenic MECP2 variants. Because the MECP2 gene is subject to X-chromosome inactivation (XCI), factors including MECP2 genotypic variation, tissue differences in XCI, and skewing of XCI all likely contribute to the clinical severity of individuals with RTT. Methods: We analyzed the XCI patterns from blood samples of 320 individuals and their mothers. It includes individuals with RTT (n = 287) and other syndromes sharing overlapping phenotypes with RTT (such as CDKL5 Deficiency Disorder [CDD, n = 16]). XCI status in each proband/mother duo and the parental origin of the preferentially inactivated X chromosome were analyzed. Results: The average XCI ratio in probands was slightly increased compared to their unaffected mothers (73% vs. 69%, p =.0006). Among the duos with informative XCI data, the majority of individuals with classic RTT had their paternal allele preferentially inactivated (n = 180/220, 82%). In sharp contrast, individuals with CDD had their maternal allele preferentially inactivated (n = 10/12, 83%). Our data indicate a weak positive correlation between XCI skewing ratio and clinical severity scale (CSS) scores in classic RTT patients with maternal allele preferentially inactivated XCI (rs = 0.35, n = 40), but not in those with paternal allele preferentially inactivated XCI (rs = −0.06, n = 180). The most frequent MECP2 pathogenic variants were enriched in individuals with highly/moderately skewed XCI patterns, suggesting an association with higher levels of XCI skewing. Conclusion: These results extend our understanding of the pathogenesis of RTT and other syndromes with overlapping clinical features by providing insight into the both XCI and the preferential XCI of parental alleles. © 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
Author KeywordsCDKL5 deficiency disorder; MECP2; preferential inactivation of parental alleles; Rett syndrome; X-chromosome inactivation
Funding detailsNational Institutes of HealthNIHNational Center for Advancing Translational SciencesNCATSEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD61222
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“Recognition language classifiers demonstrate far transfer of learning” (2022) Psychonomic Bulletin and Review
Recognition language classifiers demonstrate far transfer of learning(2022) Psychonomic Bulletin and Review, .
Dobbins, I.G.
Department of Psychological and Brain Sciences, Washington University in Saint Louis, One Brookings Drive, Saint Louis, MO 63130, United States
AbstractMachine learners trained on verbal justifications of recognition decisions reliably predict recognition accuracy. If these recognition language classifiers are recollection sensitive, they should generalize beyond the single-item, verbal recognition paradigms upon which they were trained. To test this, three classifiers were trained to distinguish justification language in three different single-item verbal recognition paradigms, learning to distinguish the language justifying hits from false alarms, high from medium confidence hits, and remember from know judgements. The resulting classifiers were then used to predictively score language justifying correct versus incorrect eyewitness lineup selections constituting a test of far transfer because of the differences in materials (faces vs. words), subject populations (undergraduate vs. online), testing procedures (single vs. multiple items), and test lengths (12 vs. hundreds of targets per subject) among others. All three classifiers reliably predicted eyewitness accuracy despite these differences. Additionally, mixed modeling demonstrated that the classifiers demonstrated both convergent and divergent validity with respect to the recollection sensitivity hypothesis. That is, they strongly predicted the accuracy of eyewitness selections (i.e., hits vs. false alarms) but failed to predict the accuracy of eyewitness rejections (i.e., correct rejections vs. misses). Moreover, one classifier was shown to predict eyewitness confidence despite being trained on a design devoid of all metacognitive judgments. These findings support the hypothesis that recognition language classifiers detect recollection conveyed in the language subjects use to justify their memory decisions. © 2022, The Psychonomic Society, Inc.
Author KeywordsAccuracy; Language; Machine learning; Recognition memory
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“A genetic mouse model with postnatal Nf1 and p53 loss recapitulates the histology and transcriptome of human malignant peripheral nerve sheath tumor” (2021) Neuro-Oncology Advances
(2021) Neuro-Oncology Advances, 3 (1), art. no. vdab129, .
Inoue, A.a , Janke, L.J.b , Gudenas, B.L.a , Jin, H.c , Fan, Y.c , Pare, J.a , Clay, M.R.b e , Northcott, P.A.a , Hirbe, A.C.d , Cao, X.a
a Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, United Statesb Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN, United Statesc Center for Applied Bioinformatics, St. Jude Children’s Research Hospital, Memphis, TN, United Statesd Division of Medical Oncology, Washington University, St. Louis, MO, United Statese Department of Pathology, University of Colorado, Aurora, CO, United States
AbstractBackground: Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas. Somatic inactivation of NF1 and cooperating tumor suppressors, including CDKN2A/B, PRC2, and p53, is found in most MPNST. Inactivation of LATS1/2 of the Hippo pathway was recently shown to cause tumors resembling MPNST histologically, although Hippo pathway mutations are rarely found in MPNST. Because existing genetically engineered mouse (GEM) models of MPNST do not recapitulate some of the key genetic features of human MPNST, we aimed to establish a GEM-MPNST model that recapitulated the human disease genetically, histologically, and molecularly. Methods: We combined 2 genetically modified alleles, an Nf1;Trp53 cis-conditional allele and an inducible Plp-CreER allele (NP-Plp), to model the somatic, possibly postnatal, mutational events in human MPNST. We also generated conditional Lats1;Lats2 knockout mice. We performed histopathologic analyses of mouse MPNST models and transcriptomic comparison of mouse models and human nerve sheath tumors. Results: Postnatal Nf1;Trp53 cis-deletion resulted in GEM-MPNST that were histologically more similar to human MPNST than the widely used germline Nf1;Trp53 cis-heterozygous (NPcis) model and showed partial loss of H3K27me3. At the transcriptome level, Nf1;p53-driven GEM-MPNST were distinct from Lats-driven GEM-MPNST and resembled human MPNST more closely than do Lats-driven tumors. Conclusions: The NP-Plp model recapitulates human MPNST genetically, histologically, and molecularly. © 2021 The Author(s). Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
Author Keywordscross-species comparison; nervous system; Schwann cells; single-sample GSEA; YAP/TAZ
Funding detailsAmerican Lebanese Syrian Associated CharitiesALSAC
Document Type: ArticlePublication Stage: FinalSource: Scopus