“A pilot investigation of emotional regulation difficulties and mindfulness-based strategies in manic and remitted bipolar I disorder and major depressive disorder” (2021) International Journal of Bipolar Disorders
A pilot investigation of emotional regulation difficulties and mindfulness-based strategies in manic and remitted bipolar I disorder and major depressive disorder
(2021) International Journal of Bipolar Disorders
Musket, C.W.a , Hansen, N.S.b , Welker, K.M.c , Gilbert, K.E.d , Gruber, J.b
a Department of Psychology, University of Pittsburgh, Pittsburgh, United States
b Department of Psychology and Neuroscience, University of Colorado, Boulder, 345 UCB, Muenzinger D321C, Boulder, CO 80309-0345, United States
c Department of Psychology, University of Massachusetts, Boston, United States
d Department of Psychiatry, Washington University in St. Louis, St. Louis, United States
Abstract
Background: Both bipolar disorder and major depressive disorder are characterized by difficulties in emotion regulation. Little is known about which specific emotion regulatory patterns may be transdiagnostic versus disorder specific, and how such patterns change as a function of current mood states. Methods: This preliminary investigation examined specific patterns of self-reported trait emotion regulation difficulties and mindfulness-based regulations strategies across four groups: remitted adults with bipolar I disorder (BD-remitted; n = 32), currently manic adults with bipolar I disorder (BD-manic; n = 19), remitted adults with major depressive disorder (MDD-remitted; n = 32), and healthy controls (CTL; n = 30). Results: All three clinical groups reported significantly greater difficulties with emotion regulation and decreased overall mindfulness-based strategies. Conclusions: These results suggest that increased emotion regulation difficulties, decreased mindfulness, and increased emotion-driven impulsivity may be transdiagnostic across mood disorders and states, and that impulsivity may be particularly impaired during periods of mania. © 2021, The Author(s).
Author Keywords
Bipolar disorder; Emotion regulation; Emotional awareness; Impulsivity; Major depressive disorder; Mindfulness
Funding details
National Alliance for Research on Schizophrenia and DepressionNARSAD
Brain and Behavior Research FoundationBBRF
National Center for Advancing Translational SciencesNCATS
National Institute of Mental HealthNIMHK23MH115074, UL1 RR024139
National Institutes of HealthNIH
National Center for Research ResourcesNCRR
Document Type: Article
Publication Stage: Final
Source: Scopus
“Change is on the horizon: call to action for the study of positive emotion and reward in psychopathology” (2021) Current Opinion in Behavioral Sciences
Change is on the horizon: call to action for the study of positive emotion and reward in psychopathology
(2021) Current Opinion in Behavioral Sciences, 39, pp. 34-40.
Villanueva, C.M.a , Silton, R.L.b , Heller, W.c , Barch, D.M.d , Gruber, J.a
a University of Colorado Boulder, United States
b Loyola University Chicago, United States
c University of Illinois Urbana-Champaign, United States
d Washington University in St. Louis, United States
Abstract
We briefly discuss current challenges in the field of positive emotion and reward in psychopathology. These include seven key ‘blind spots’ including: (1) breaking down silos and barriers among disciplines, (2) paradigm shifts in understanding positive emotion, (3) rethinking our language of positive emotions, (4) increasing diversity of research approaches and perspectives, (5) capturing positive emotions in real-world settings, (6) confronting the key role of substance use in positive emotion regulation, and (7) embracing lifespan developmental approaches. By highlighting these challenges, we aim to generate discussion and enhance opportunities for synergistic collaboration as our field looks ahead to dynamic changes and fruitful advances on the horizon. © 2020 Elsevier Ltd
Document Type: Review
Publication Stage: Final
Source: Scopus
“Clinical validation of combinatorial pharmacogenomic testing and single-gene guidelines in predicting psychotropic medication blood levels and clinical outcomes in patients with depression” (2021) Psychiatry Research
Clinical validation of combinatorial pharmacogenomic testing and single-gene guidelines in predicting psychotropic medication blood levels and clinical outcomes in patients with depression
(2021) Psychiatry Research, 296, art. no. 113649, .
Rothschild, A.J.a , Parikh, S.V.b , Hain, D.c , Law, R.c , Thase, M.E.d , Dunlop, B.W.e , DeBattista, C.f , Conway, C.R.g , Forester, B.P.h i , Shelton, R.C.j , Macaluso, M.j , Brown, K.k , Lewis, D.c , Gutin, A.k , Jablonski, M.R.c , Greden, J.F.b
a University of Massachusetts Medical School and UMass Memorial Healthcare, Worcester, MA 01655, United States
b University of Michigan Comprehensive Depression Center and Department of Psychiatry, and National Network of Depression Centers, Ann Arbor, MI 48109, United States
c Myriad Neuroscience, Mason, OH 45040, United States
d Perelman School of Medicine of the University of Pennsylvania and the Corporal Michael Crescenz VAMC, Philadelphia, PA 19104, United States
e Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30329, United States
f Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, United States
g Department of Psychiatry, Washington University School of Medicine, and the John Cochran Veteran’s Administration Hospital, St. Louis, MO 63110, United States
h McLean Hospital, Division of Geriatric Psychiatry, Belmont, MA 02478, United States
i Harvard Medical School, Boston, MA, United States
j Department of Psychiatry and Behavioral Neurobiology and School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, United States
k Myriad Genetics, Inc., Salt Lake City, UT 84108, United States
Abstract
We evaluated the clinical validity of a combinatorial pharmacogenomic test and single-gene Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines against patient outcomes and medication blood levels to assess their ability to inform prescribing in major depressive disorder (MDD). This is a secondary analysis of the Genomics Used to Improve DEpression Decisions (GUIDED) randomized-controlled trial, which included patients with a diagnosis of MDD, and ≥1 prior medication failure. The ability to predict increased/decreased medication metabolism was validated against blood levels at screening (adjusted for age, sex, smoking status). The ability of predicted gene-drug interactions (pharmacogenomic test) or therapeutic recommendations (single-gene guidelines) to predict patient outcomes was validated against week 8 outcomes (17-item Hamilton Depression Rating Scale; symptom improvement, response, remission). Analyses were performed for patients taking any eligible medication (outcomes N=1,022, blood levels N=1,034) and the subset taking medications with single-gene guidelines (outcomes N=584, blood levels N=372). The combinatorial pharmacogenomic test was the only significant predictor of patient outcomes. Both the combinatorial pharmacogenomic test and single-gene guidelines were significant predictors of blood levels for all medications when evaluated separately; however, only the combinatorial pharmacogenomic test remained significant when both were included in the multivariate model. There were no substantial differences when all medications were evaluated or for the subset with single-gene guidelines. Overall, this evaluation of clinical validity demonstrates that the combinatorial pharmacogenomic test was a superior predictor of patient outcomes and medication blood levels when compared with guidelines based on individual genes. © 2020
Author Keywords
Clinical validity; Combinatorial pharmacogenomics; CPIC guidelines; Depression; GeneSight; Medication blood levels; Pharmacokinetics
Funding details
Otsuka PharmaceuticalOPC
Ontario Brain InstituteOBI
Ethel and James Flinn Foundation
National Institutes of HealthNIH
Pfizer
Eli Lilly and Company
Foundation for Barnes-Jewish Hospital
Takeda Pharmaceuticals North AmericaTPNA
Biogen
Stanley Medical Research InstituteSMRI
Janssen Biotech
National Institute of Mental HealthNIMH
Canadian Institutes of Health ResearchCIHR
Assurex Health
ACADIA PharmaceuticalsACADIA
Allergan
Myriad Genetics
Document Type: Article
Publication Stage: Final
Source: Scopus
“Screen use before bedtime: Consequences for nighttime sleep in young children” (2021) Infant Behavior and Development
Screen use before bedtime: Consequences for nighttime sleep in young children
(2021) Infant Behavior and Development, 62, art. no. 101522, .
Staples, A.D.a , Hoyniak, C.b , McQuillan, M.E.c , Molfese, V.d , Bates, J.E.e
a Eastern Michigan University, United States
b Washington University in St. Louis School of Medicine, United States
c Indiana University School of Medicine, United States
d University of Nebraska–Lincoln, United States
e Indiana University–Bloomington, United States
Abstract
There is increasing interest in the relation between screen use and sleep problems in early childhood. In a sample of 30-month-old children, this study used observational measures of screen use during the hour or so leading up to bedtime, parent reports of screen use during the child’s bedtime routine, and actigraphic measures of toddler sleep to complement parent-reported sleep problems. Whether screen use was observed during the pre-bedtime period or was reported by the parents as part of the nightly bedtime routine, greater screen use in either context was associated with more parent-reported sleep problems. Additionally, more frequent parent-reported screen use during the bedtime routine was also associated with actigraphic measures of later sleep, shorter sleep, and more night-to-night variability in duration and timing of sleep. These associations suggest the negative consequences of screen use for children’s sleep extend both to aspects of sleep reported by parents (e.g., bedtime resistance, signaled awakenings) and to aspects measured by actigraphy (e.g., shorter and more variable sleep). © 2020 Elsevier Inc.
Author Keywords
Actigraphy; Bedtime routines; Early childhood; Screen use; Sleep
Funding details
National Institute of Mental HealthNIMHHD073202, T32 MH100019-06
Document Type: Article
Publication Stage: Final
Source: Scopus
“Personality Pathology and Substance Misuse in Later Life: Perspectives from Interviewer-, Self-, and Informant-Reports” (2021) Journal of Psychopathology and Behavioral Assessment
Personality Pathology and Substance Misuse in Later Life: Perspectives from Interviewer-, Self-, and Informant-Reports
(2021) Journal of Psychopathology and Behavioral Assessment, .
Paul, S.E.a , Winograd, R.P.b , Oltmanns, T.F.a
a Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, 1125 One Brookings Drive, St. Louis, MO 63130, United States
b Missouri Institute of Mental Health, St. Louis, MO, United States
Abstract
Research indicates a robust association between personality and substance use and misuse. The high prevalence and pervasive detrimental impacts of alcohol use disorder (AUD) and smoking of tobacco necessitate more studies designed to identify factors closely associated with these outcomes in specific populations. The analyses reported in the present paper concern the relative utilities of five measures of personality and personality pathology rated by three sources (self, informant, and interviewer) in predicting AUD and regular smoking in a representative sample of 987 older adults, an understudied and uniquely vulnerable population. All measures and sources contributed to the predictions, with notable parallels as well as some important differences identified across substances and sources of information. In particular, low agreeableness robustly predicted AUD and smoking across self- and informant-reports. High interviewer-rated borderline personality pathology also strongly predicted AUD. Model fit indices suggested that measures of personality and personality pathology have stronger utility in predicting AUD as compared to regular smoking. These findings have important implications for the assessment of older adults in research and clinical settings and for the understanding of enduring risk factors for substance misuse later in life. Multi-source personality information is valuable for generating a complete picture of the relationship between personality and substance misuse. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.
Author Keywords
Alcohol use disorder; Informant-reports; Multisource assessment; Personality; Personality pathology; Smoking
Funding details
National Institute on AgingNIA
National Institute on AgingNIARO1-AG045231, RO1-AG056517
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Loss of Consciousness in the Young Child” (2021) Pediatric Cardiology
Loss of Consciousness in the Young Child
(2021) Pediatric Cardiology, .
Villafane, J.a l , Miller, J.R.b , Glickstein, J.c , Johnson, J.N.d , Wagner, J.e , Snyder, C.S.f , Filina, T.g , Pomeroy, S.L.g , Sexson-Tejtel, S.K.h , Haxel, C.i , Gottlieb, J.j , Eghtesady, P.b , Chowdhury, D.k
a Department of Pediatrics, University of Cincinnati and Cincinnati Children’s Hospital, Cincinnati, OH, United States
b Department of Surgery, Division of Cardiothoracic Surgery, St. Louis Children’s Hospital, Washington University School of Medicine, St. Louis, MO, United States
c Department of Pediatrics, Columbia University Medical Center, New York-Presbyterian Hospital, New York, NY, United States
d Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN, United States
e Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO, United States
f Congenital Heart Collaborative, Rainbow Babies and Children’s Hospital, Case Western University, Cleveland, OH, United States
g Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
h Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States
i Department of Pediatrics, Children’s Hospital of Colorado, University of Colorado School of Medicine, Aurora, CO, United States
j Lancaster Pediatric Associates, Lancaster, PA, United States
k Cardiology Care for Children, Lancaster, PA, United States
l Department of Pediatrics, 743 East Broadway, Suite 300, Louisville, KY 40202, United States
Abstract
In the very young child (less than eight years of age), transient loss of consciousness represents a diagnostic and management dilemma for clinicians. While most commonly benign, syncope may be due to cardiac dysfunction which can be life-threatening. It can be secondary to an underlying ion channelopathy, cardiac inflammation, cardiac ischemia, congenital heart disease, cardiomyopathy, or pulmonary hypertension. Patients with genetic disorders require careful evaluation for a cardiac cause of syncope. Among the noncardiac causes, vasovagal syncope is the most common etiology. Breath-holding spells are commonly seen in this age group. Other causes of transient loss of consciousness include seizures, neurovascular pathology, head trauma, psychogenic pseudosyncope, and factitious disorder imposed on another and other forms of child abuse. A detailed social, present, past medical, and family medical history is important when evaluating loss of consciousness in the very young. Concerning characteristics of syncope include lack of prodromal symptoms, no preceding postural changes or occurring in a supine position, after exertion or a loud noise. A family history of sudden unexplained death, ion channelopathy, cardiomyopathy, or congenital deafness merits further evaluation. Due to inherent challenges in diagnosis at this age, often there is a lower threshold for referral to a specialist. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.
Author Keywords
Loss of consciousness; Pediatric; Syncope; Young child
Document Type: Review
Publication Stage: Article in Press
Source: Scopus
“Social class discrimination as a predictor of first cigarette use and transition to nicotine use disorder in Black and White youth” (2021) Social Psychiatry and Psychiatric Epidemiology
Social class discrimination as a predictor of first cigarette use and transition to nicotine use disorder in Black and White youth
(2021) Social Psychiatry and Psychiatric Epidemiology, .
Sartor, C.E.a b , Haeny, A.M.a , Ahuja, M.c , Bucholz, K.K.b
a Department of Psychiatry, Yale School of Medicine, 389 Whitney Avenue, New Haven, CT 06511, United States
b Department of Psychiatry, Washington University School of Medicine, 660 Euclid Avenue, St. Louis, MO 63116, United States
c Department of Health Services Management and Policy, East Tennessee State University, College of Public Health, J1276 Gilbreath Drive, Johnson City, TN 37614, United States
Abstract
Purpose: To characterize the association of social class discrimination with the timing of first cigarette use and progression to DSM-IV nicotine dependence (ND) in Black and White youth, examining variation by race, parent vs. youth experiences of discrimination, socioeconomic status (SES), and stage of smoking. Methods: Data were drawn from 1461 youth (55.2% Black, 44.8% White; 50.2% female) and mothers in a high-risk family study of alcohol use disorder and related conditions. Cox proportional hazard regression analyses were conducted, using youth’s and mother’s social class discrimination to predict first cigarette use and progression to ND, stratifying by race. Interactions between discrimination and SES indicators (parental education and household income) were tested. Adjusted models included psychiatric covariates. Results: In the adjusted first cigarette use models, neither youth’s nor mother’s social class discrimination was a significant predictor among Black youth, but mother’s discrimination was associated with increased risk [HR = 1.53 (1.18–1.99)] among White youth. In the adjusted ND models, mother’s discrimination was associated with reduced ND risk for Black youth in middle-income families [HR = 0.29 (CI 0.13–0.63)], but neither youth’s nor mother’s discrimination predicted transition to ND among White youth. Conclusions: The observed race and smoking stage-specific effects suggest that social class discrimination is more impactful on early stages of smoking for White youth and later stages for Black youth. The robustness of links with mother’s discrimination experiences further suggests the importance of considering family-level effects and the need to explore possible mechanisms, such as socialization processes. © 2021, Springer-Verlag GmbH Germany, part of Springer Nature.
Author Keywords
Black/African American; Cigarette smoking; Discrimination; Socioeconomic status
Funding details
National Institute on Drug AbuseNIDADA019426
National Institute on Alcohol Abuse and AlcoholismNIAAAAA023549, AA12640
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Parkinson’s disease – What’s the fus?” (2020) New England Journal of Medicine
Parkinson’s disease – What’s the fus?
(2020) New England Journal of Medicine, 383 (26), pp. 2582-2584.
Perlmutter, J.S., Ushe, M.
The Washington University School of Medicine, St. Louis, United States
Document Type: Editorial
Publication Stage: Final
Source: Scopus
“Intensive Teenage Activity Is Associated With Greater Muscle Hyperintensity on T1W Magnetic Resonance Imaging in Adults With Dysferlinopathy” (2020) Frontiers in Neurology
Intensive Teenage Activity Is Associated With Greater Muscle Hyperintensity on T1W Magnetic Resonance Imaging in Adults With Dysferlinopathy
(2020) Frontiers in Neurology, 11, art. no. 613446, .
Moore, U.a , Jacobs, M.b c , Fernandez-Torron, R.a , LLauger Rossello, J.d , Smith, F.E.e , James, M.a , Mayhew, A.a , Rufibach, L.f , Carlier, P.G.g , Blamire, A.M.e , Day, J.W.h , Jones, K.J.i , Bharucha-Goebel, D.X.j k , Salort-Campana, E.l , Pestronk, A.m , Walter, M.C.n , Paradas, C.o p , Stojkovic, T.q , Mori-Yoshimura, M.r , Bravver, E.s , Pegoraro, E.t , Mendell, J.R.u , The Jain COS Consortiumx , Bushby, K.a , Straub, V.a , Diaz-Manera, J.a v w
a The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
b Division of Biostatistics and Study Methodology, Center for Translational Science, Children’s National Health System, Washington, DC, United States
c Pediatrics, Epidemiology and Biostatistics, George Washington University, Washington, DC, United States
d Radiology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
e Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
f Jain Foundation, Newcastle upon Tyne, Seattle, WA, United States
g Université Paris-Saclay, CEA, DRF, Service Hospitalier Frederic Joliot, Orsay, France
h Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States
i The Children’s Hospital at Westmead, The University of Sydney, Sydney, NSW, Australia
j Department of Neurology Children’s National Health System, Washington, DC, United States
k National Institutes of Health (NINDS), Bethesda, MD, United States
l Service des maladies neuromusculaire et de la SLA, Hôpital de La Timone, Marseille, France
m Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
n Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-University of Munich, Munich, Germany
o Center for Biomedical Network Research on Eurodegenerative Diseases, Instituto de Salud Carlos III, Madrid, Spain
p Neuromuscular Unit, Department of Neurology, Hospital U. Virgen del Rocío/Instituto de Biomedicina de Sevilla, Sevilla, Spain
q Centre de référence des maladies neuromusculaires, Institut de Myologie, AP-HP, Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France
r Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry Tokyo, Tokyo, Japan
s Carolinas Neuromuscular/ALS-MDA Center, Neuroscience Institute, Carolinas HealthCare System, Charlotte, NC, United States
t Department of Neuroscience, University of Padova, Padova, Italy
u The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, United States
v Neuromuscular disorders Unit, Department of Neurology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain
w Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Valencia, Spain
Abstract
Practice of sports during childhood or adolescence correlates with an earlier onset and more rapidly progressing phenotype in dysferlinopathies. To determine if this correlation relates to greater muscle pathology that persists into adulthood, we investigated the effect of exercise on the degree of muscle fatty replacement measured using muscle MRI. We reviewed pelvic, thigh and leg T1W MRI scans from 160 patients with genetically confirmed dysferlinopathy from the Jain Foundation International clinical outcomes study in dysferlinopathy. Two independent assessors used the Lamminen-Mercuri visual scale to score degree of fat replacement in each muscle. Exercise intensity for each individual was defined as no activity, minimal, moderate, or intensive activity by using metabolic equivalents and patient reported frequency of sports undertaken between the ages of 10 and 18. We used ANCOVA and linear modeling to compare the mean Lamminen-Mercuri score for the pelvis, thigh, and leg between exercise groups, controlling for age at assessment and symptom duration. Intensive exercisers showed greater fatty replacement in the muscles of the pelvis than moderate exercisers, but no significant differences of the thigh or leg. Within the pelvis, Psoas was the muscle most strongly associated with this exercise effect. In patients with a short symptom duration of <15 years there was a trend toward greater fatty replacement in the muscles of the thigh. These findings define key muscles involved in the exercise-phenotype effect that has previously been observed only clinically in dysferlinopathy and support recommendations that pre-symptomatic patients should avoid very intensive exercise. © Copyright © 2020 Moore, Jacobs, Fernandez-Torron, LLauger Rossello, Smith, James, Mayhew, Rufibach, Carlier, Blamire, Day, Jones, Bharucha-Goebel, Salort-Campana, Pestronk, Walter, Paradas, Stojkovic, Mori-Yoshimura, Bravver, Pegoraro, Mendell, Bushby, Straub and Diaz-Manera.
Author Keywords
dysferlinopathy; exercise; LGMDR2; limb girdle muscle dystrophy; Magnetic Resonace Imaging (MRI); Miyoshi myopathy
Funding details
Medical Research CouncilMRC
MR/S005021/1
Jain Foundation
Biogen
Jain Foundation
Document Type: Article
Publication Stage: Final
Source: Scopus
“NEWTON-2 Cisternal (Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage): A Phase 2, Multicenter, Randomized, Open-Label Safety Study of Intracisternal EG-1962 in Aneurysmal Subarachnoid Hemorrhage” (2020) Neurosurgery
NEWTON-2 Cisternal (Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage): A Phase 2, Multicenter, Randomized, Open-Label Safety Study of Intracisternal EG-1962 in Aneurysmal Subarachnoid Hemorrhage
(2020) Neurosurgery, 88 (1), pp. E13-E26.
Macdonald, R.L.a b , Hänggi, D.c , Ko, N.U.d , Darsaut, T.E.e , Carlson, A.P.f , Wong, G.K.g , Etminan, N.h , Mayer, S.A.i , Aldrich, E.F.j , Diringer, M.N.k , Ng, D.l , Strange, P.m , Bleck, T.n , Grubb, R.j , Suarez, J.I.o p q
a Department of Neurological Surgery, University of California, San Francisco, Fresno, California
b NJ
c Department of Neurosurgery, Düsseldorf University Hospital, Heinrich-Heine-Universität, Düsseldorf, Germany
d Department of Neurology, University of California, San Francisco, CA, Mexico
e Division of Neurosurgery, Department of Surgery, University of Alberta, Edmonton, Canada
f Department of Neurosurgery, University of New Mexico School of Medicine, Albuquerque, NM, United States
g Division of Neurosurgery, Department of Surgery, Chinese University of Hong Kong, Hong Kong, China
h University Medical Center Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany
i Department of Neurology, Wayne State University School of Medicine, Detroit, MI, United States
j Neurological Surgery, University of Maryland Medical Center, Baltimore, MD, United States
k Neurological Critical Care, Washington University School of Medicine, St. Louis, MO, United States
l Austin, TX, United States
m Integrated Medical Development LLC, Princeton, NJ, United States
n Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, IL, Mexico
o Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
p Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
q Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Abstract
BACKGROUND: A sustained release microparticle formulation of nimodipine (EG-1962) was developed for treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE: To assess safety, tolerability, and pharmacokinetics of intracisternal EG-1962 in an open-label, randomized, phase 2 study of up to 12 subjects. METHODS: Subjects were World Federation of Neurological Surgeons grades 1 to 2, modified Fisher grades 2 to 4, and underwent aneurysm clipping within 48 h of aSAH. EG-1962, containing 600 mg nimodipine, was administered into the basal cisterns. Outcome on the extended Glasgow Outcome Scale (eGOS), pharmacokinetics, delayed cerebral ischemia and infarction, rescue therapy, and safety were evaluated. RESULTS: The study was halted when a phase 3 study of intraventricular EG-1962 stopped because that study was unlikely to meet its primary endpoint. Six subjects were randomized (5 EG-1962 and 1 oral nimodipine). After 90-d follow-up, favorable outcome on the eGOS occurred in 1 of 5 EG-1962 and in the single oral nimodipine patient. Four EG-1962 and the oral nimodipine subject had angiographic vasospasm. One EG-1962 subject had delayed cerebral ischemia, and all subjects with angiographic vasospasm received rescue therapy except 1 EG-1962 patient. One subject treated with EG-1962 developed right internal carotid and middle cerebral artery narrowing 5 mo after placement of EG-1962, leading to occlusion and cerebral infarction. Pharmacokinetics showed similar plasma concentrations of nimodipine in both groups. CONCLUSION: Angiographic vasospasm and unfavorable clinical outcome still occurred after placement of EG-1962. Internal carotid artery narrowing and occlusion after placement of EG-1962 in the basal cisterns has not been reported. Copyright © 2020 by the Congress of Neurological Surgeons.
Author Keywords
aSAH; Cerebral aneurysm; Clinical trial; Delayed cerebral ischemia; Extended release; Nimodipine; Subarachnoid hemorrhage
Document Type: Article
Publication Stage: Final
Source: Scopus
“Using Histopathology to Assess the Reliability of Intraoperative Magnetic Resonance Imaging in Guiding Additional Brain Tumor Resection: A Multicenter Study” (2020) Neurosurgery
Using Histopathology to Assess the Reliability of Intraoperative Magnetic Resonance Imaging in Guiding Additional Brain Tumor Resection: A Multicenter Study
(2020) Neurosurgery, 88 (1), pp. E49-E59.
Shah, A.S.a , Yahanda, A.T.a , Sylvester, P.T.a , Evans, J.a , Dunn, G.P.a , Jensen, R.L.b , Honeycutt, J.c , Cahill, D.P.d , Sutherland, G.R.e , Oswood, M.f g , Shah, M.h , Abram, S.R.i , Rich, K.M.a , Dowling, J.L.a , Leuthardt, E.C.a , Dacey, R.G.a , Kim, A.H.a , Zipfel, G.J.a , Limbrick, D.D.a , Smyth, M.D.a , Leonard, J.j , Chicoine, M.R.a
a Washington University School of Medicine, St. Louis, MO, United States
b Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, United States
c Cook Children’s Hospital, Fort Worth, TX, United States
d Massachusetts General Hospital, Boston, MA
e University of Calgary, Calgary, Canada
f University of Minnesota, Minneapolis, MN, United States
g Allina Health, Minneapolis, MN, United States
h Goodman Campbell and Indiana University, Indianapolis, IN, United States
i St. Thomas Hospital, Nashville, TN, United States
j Department of Neurosurgery, Nationwide Children’s Hospital, Columbus, OH, United States
Abstract
BACKGROUND: Intraoperative magnetic resonance imaging (iMRI) is a powerful tool for guiding brain tumor resections, provided that it accurately discerns residual tumor. OBJECTIVE: To use histopathology to assess how reliably iMRI may discern additional tumor for a variety of tumor types, independent of the indications for iMRI. METHODS: A multicenter database was used to calculate the odds of additional resection during the same surgical session for grade I to IV gliomas and pituitary adenomas. The reliability of iMRI for identifying residual tumor was assessed using histopathology of tissue resected after iMRI. RESULTS: Gliomas (904/1517 cases, 59.6%) were more likely than pituitary adenomas (176/515, 34.2%) to receive additional resection after iMRI (P < .001), but these tumors were equally likely to have additional tissue sent for histopathology (398/904, 44.4% vs 66/176, 37.5%; P = .11). Tissue samples were available for resections after iMRI for 464 cases, with 415 (89.4%) positive for tumor. Additional resections after iMRI for gliomas (361/398, 90.7%) were more likely to yield additional tumor compared to pituitary adenomas (54/66, 81.8%) (P = .03). There were no significant differences in resection after iMRI yielding histopathologically positive tumor between grade I (58/65 cases, 89.2%; referent), grade II (82/92, 89.1%) (P = .98), grade III (72/81, 88.9%) (P = .95), or grade IV gliomas (149/160, 93.1%) (P = .33). Additional resection for previously resected tumors (122/135 cases, 90.4%) was equally likely to yield histopathologically confirmed tumor compared to newly-diagnosed tumors (293/329, 89.0%) (P = .83). CONCLUSION: Histopathological analysis of tissue resected after use of iMRI for grade I to IV gliomas and pituitary adenomas demonstrates that iMRI is highly reliable for identifying residual tumor. Copyright © 2020 by the Congress of Neurological Surgeons.
Author Keywords
Additional resection; Glioma; Histopathology; iMRI; Intraoperative MRI; Pituitary; Pituitary adenoma; Resection; Tumor
Document Type: Article
Publication Stage: Final
Source: Scopus
“Associations Between Atrial Cardiopathy and Cerebral Amyloid: The ARIC-PET Study” (2020) Journal of the American Heart Association
Associations Between Atrial Cardiopathy and Cerebral Amyloid: The ARIC-PET Study
(2020) Journal of the American Heart Association, 9 (24), p. e018399.
Johansen, M.C.a , Mosley, T.H.b , Knopman, D.S.c , Wong, D.F.d , Ndumele, C.a , Shah, A.M.e , Solomon, S.D.e , Gottesman, R.F.a
a Johns Hopkins University School of Medicine Baltimore MD
b University of Mississippi Medical Center Jackson MS
c Mayo Clinic Rochester MN
d Washington University in St. Louis School of Medicine St. Louis MO
e Brigham and Women’s Hospital Boston MA
Abstract
Background Atrial fibrillation (AF) is a risk factor for cognitive decline, possibly from silent brain infarction. Left atrial changes in structure or function (atrial cardiopathy) can lead to AF but may impact cognition independently. It is unknown if AF or atrial cardiopathy also acts on Alzheimer disease-specific mechanisms, such as deposition of β-amyloid. Methods and Results A total of 316 dementia-free participants from the ARIC (Atherosclerosis Risk in Communities) study underwent florbetapir positron emission tomography, electrocardiography, and 2-dimensional echocardiography. Atrial cardiopathy was defined as ≥1: (1) left atrial volume index >34 mL/m2; (2) P-wave terminal force >5000 µV×ms; and (3) serum NT-proBNP (N-terminal pro-B-type natriuretic peptide) >250 pg/mL. Cross-sectional associations between global cortical β-amyloid (>1.2 standardized uptake value ratio) and adjudicated history of AF and atrial cardiopathy, each, were evaluated using multivariable logistic regression. Participants (mean age, 76 years) were 56% women and 42% Black individuals. Odds of elevated florbetapir standardized uptake value ratio were significantly increased among those with atrial cardiopathy (odds ratio, 1.81; 95% CI, 1.02-3.22) and doubled for those with enlarged left atrial volume index after adjustment for demographics/risk factors (95% CI, 1.04-4.61). There was no association between P-wave terminal force or NT-proBNP and elevated florbetapir standardized uptake value ratio, nor between AF and elevated standardized uptake value ratio. Conclusions Among healthy, nondemented community-dwelling older individuals, we report an association between atrial cardiopathy, left atrial volume index, and elevated brain amyloid, by positron emission tomography, without a similar association in individuals with AF. Potential limitations include reverse causation and survival bias. Ongoing work will help determine if changes in cardiac structure and function precede or occur simultaneously with amyloid deposition.
Author Keywords
atrial cardiopathy; cognitive decline; cohort study; positron emission tomography
Document Type: Article
Publication Stage: Final
Source: Scopus
“Impact of Intraoperative Magnetic Resonance Imaging and Other Factors on Surgical Outcomes for Newly Diagnosed Grade II Astrocytomas and Oligodendrogliomas: A Multicenter Study” (2020) Neurosurgery
Impact of Intraoperative Magnetic Resonance Imaging and Other Factors on Surgical Outcomes for Newly Diagnosed Grade II Astrocytomas and Oligodendrogliomas: A Multicenter Study
(2020) Neurosurgery, 88 (1), pp. 63-73.
Yahanda, A.T.a , Patel, B.a , Shah, A.S.a , Cahill, D.P.b , Sutherland, G.c , Honeycutt, J.d , Jensen, R.L.e , Rich, K.M.a , Dowling, J.L.a , Limbrick, D.D.a , Dacey, R.G.a , Kim, A.H.a , Leuthardt, E.C.a , Dunn, G.P.a , Zipfel, G.J.a , Leonard, J.R.f , Smyth, M.D.a , Shah, M.V.g , Abram, S.R.h , Evans, J.a , Chicoine, M.R.a
a Department of Neurosurgery, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
b Department of Neurological Surgery, Massachusetts General Hospital, Boston, MA
c Department of Neurological Surgery, University of Calgary School of Medicine, Calgary, Canada
d Department of Neurological Surgery, Cook Children’s Medical Center, Fort Worth, TX, United States
e Department of Neurological Surgery, University of Utah School of Medicine, Salt Lake City, UT, United States
f Department of Neurological Surgery, Ohio State University College of Medicine, Columbus, OH, United States
g Department of Neurological Surgery, Goodman Campbell Brain and Spine, Indianapolis, IN, United States
h Department of Neurological Surgery, St. Thomas Hospital, Nashville, TN, United States
Abstract
BACKGROUND: Few studies use large, multi-institutional patient cohorts to examine the role of intraoperative magnetic resonance imaging (iMRI) in the resection of grade II gliomas. OBJECTIVE: To assess the impact of iMRI and other factors on overall survival (OS) and progression-free survival (PFS) for newly diagnosed grade II astrocytomas and oligodendrogliomas. METHODS: Retrospective analyses of a multicenter database assessed the impact of patient-, treatment-, and tumor-related factors on OS and PFS. RESULTS: A total of 232 resections (112 astrocytomas and 120 oligodendrogliomas) were analyzed. Oligodendrogliomas had longer OS (P < .001) and PFS (P = .01) than astrocytomas. Multivariate analyses demonstrated improved OS for gross total resection (GTR) vs subtotal resection (STR; P = .006, hazard ratio [HR]: .23) and near total resection (NTR; P = .02, HR: .64). GTR vs STR (P = .02, HR: .54), GTR vs NTR (P = .04, HR: .49), and iMRI use (P = .02, HR: .54) were associated with longer PFS. Frontal (P = .048, HR: 2.11) and occipital/parietal (P = .003, HR: 3.59) locations were associated with shorter PFS (vs temporal). Kaplan-Meier analyses showed longer OS with increasing extent of surgical resection (EOR) (P = .03) and 1p/19q gene deletions (P = .02). PFS improved with increasing EOR (P = .01), GTR vs NTR (P = .02), and resections above STR (P = .04). Factors influencing adjuvant treatment (35.3% of patients) included age (P = .002, odds ratio [OR]: 1.04) and EOR (P = .003, OR: .39) but not glioma subtype or location. Additional tumor resection after iMRI was performed in 105/159 (66%) iMRI cases, yielding GTR in 54.5% of these instances. CONCLUSION: EOR is a major determinant of OS and PFS for patients with grade II astrocytomas and oligodendrogliomas. Intraoperative MRI may improve EOR and was associated with increased PFS. Copyright © 2020 by the Congress of Neurological Surgeons.
Author Keywords
Astrocytoma; Extent of resection; Grade II glioma; Intraoperative magnetic resonance imaging; Low-grade glioma; Oligodendroglioma
Document Type: Article
Publication Stage: Final
Source: Scopus
“A Review of Passive Brain Mapping Techniques in Neurological Surgery” (2020) Neurosurgery
A Review of Passive Brain Mapping Techniques in Neurological Surgery
(2020) Neurosurgery, 88 (1), pp. 15-24.
Roland, J.L.a , Hacker, C.D.b , Leuthardt, E.C.b
a Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, Mexico
b Department of Neurological Surgery, Washington University in St Louis, St Louis, MO, United States
Abstract
Brain mapping is a quintessential part of neurosurgical practice. Accordingly, much of our understanding of the brain’s functional organization, and in particular the motor homunculus, is largely attributable to the clinical investigations of past neurosurgeons. Traditionally mapping was invasive and involved the application of electrical current to the exposed brain to observe focal disruption of function or to elicit overt actions. More recently, a wide variety of techniques have been developed that do not require electrical stimulation and often do not require any explicit participation by the subject. Collectively we refer to these as passive mapping modalities. Here we review the spectrum of passive mapping used by neurosurgeons for mapping and surgical planning that ranges from invasive intracranial recordings to noninvasive imaging as well as regimented task-based protocols to completely task-free paradigms that can be performed intraoperatively while under anesthesia. Copyright © 2020 by the Congress of Neurological Surgeons.
Author Keywords
Brain mapping; Electrophysiology; Functional MRI; Passive mapping; Resting state
Document Type: Article
Publication Stage: Final
Source: Scopus
“Preemptive Analgesic Effect of Intrathecal Applications of Neuroactive Steroids in a Rodent Model of Post-Surgical Pain: Evidence for the Role of T-Type Calcium Channels” (2020) Cells
Preemptive Analgesic Effect of Intrathecal Applications of Neuroactive Steroids in a Rodent Model of Post-Surgical Pain: Evidence for the Role of T-Type Calcium Channels
(2020) Cells, 9 (12), .
Tat, Q.L.a , Joksimovic, S.M.a , Krishnan, K.b , Covey, D.F.b c , Todorovic, S.M.a d , Jevtovic-Todorovic, V.a
a Department of Anesthesiology, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States
b Department of Developmental Biology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
c Taylor Family Institute for Innovative Psychiatric Research, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
d Neuroscience Graduate Program, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States
Abstract
Preemptive management of post-incisional pain remains challenging. Here, we examined the role of preemptive use of neuroactive steroids with activity on low-voltage activated T-type Ca2+ channels (T-channels) and γ-aminobutyric acid A (GABAA) receptors in the development and maintenance of post-incisional pain. We use neuroactive steroids with distinct effects on GABAA receptors and/or T-channels: Alphaxalone (combined GABAergic agent and T-channel inhibitor), ECN (T-channel inhibitor), CDNC24 (GABAergic agent), and compared them with an established analgesic, morphine (an opioid agonist without known effect on either T-channels or GABAA receptors). Adult female rats sustained the skin and muscle incision on the plantar surface of the right paw. We injected the agents of choice intrathecally either before or after the development of post-incisional pain. The pain development was monitored by studying mechanical hypersensitivity. Alphaxalone and ECN, but not morphine, are effective in alleviating mechanical hyperalgesia when administered preemptively whereas morphine provides dose-dependent pain relief only when administered once the pain had developed. CDNC24 on the other hand did not offer any analgesic benefit. Neuroactive steroids that inhibit T-currents-Alphaxalone and ECN-unlike morphine, are effective preemptive analgesics that may offer a promising therapeutic approach to the treatment of post-incisional pain, especially mechanical hypersensitivity.
Author Keywords
adult female rats; GABAergic; incision pain; mechanical hypersensitivity; morphine; voltage-gated calcium channels
Document Type: Article
Publication Stage: Final
Source: Scopus
“Assessment of Plasma Amyloid-β42/40 and Cognitive Decline Among Community-Dwelling Older Adults” (2020) JAMA Network Open
Assessment of Plasma Amyloid-β42/40 and Cognitive Decline Among Community-Dwelling Older Adults
(2020) JAMA Network Open, 3 (12), p. e2028634.
Giudici, K.V.a , de Souto Barreto, P.a b , Guyonnet, S.a b , Li, Y.c d , Bateman, R.J.c , Vellas, B.a b , MAPT/DSA Groupe
a Gerontopole of Toulouse, Institute of Ageing, Toulouse University Hospital, Toulouse, France
b University of Toulouse III, Toulouse, France
c Department of Neurology, Washington University School of Medicine in St Louis, St Louis, MO, United States
d Division of Biostatistics, Washington University School of Medicine in St Louis, St Louis, MO, United States
Abstract
Importance: Plasma measurement of amyloid-β (Aβ) peptides has been associated with cognitive function, but evidence of its ability to identify cognitive decline is still scarce. Objective: To investigate the associations between plasma Aβ42/40 and cognitive decline over time among community-dwelling older adults with subjective memory concerns. Design, Setting, and Participants: This multicenter cohort study used data from volunteers in the 5-year study Multidomain Alzheimer Preventive Trial (MAPT). Participants were aged 70 years or older and observed for a median (interquartile range) of 3.9 (2.0-4.0) years. Recruitment of participants started in May 2008 and ended in February 2011. Follow-up ended in April 2016. Data analysis was conducted from April to October 2020. Exposure: Plasma Aβ42 and Aβ40 were measured at 12 months for 448 participants (92.8%) and at 24 months for the rest. The moment of Aβ assessment was defined as the baseline for this study. Main Outcomes and Measures: Cognitive function was assessed at 12, 24, 36, 48, and 60 months by a composite cognitive score based on 4 tests; Mini Mental State Examination (MMSE); Clinical Dementia Rating, sum of boxes; and Alzheimer Disease Cooperative Study-Activities of Daily Living. Mixed-effect linear regressions were performed. Results: A total of 483 participants (median [IQR] age, 76.0 [73.0-80.0]; 286 [59.2%] women) were analyzed. Of them, 161 (33.3%) were classified as low plasma Aβ42/40 (≤0.107). After adjusting for age, sex, education, body mass index, Geriatric Depression Scale score, apolipoprotein E ε4 genotype, and MAPT intervention groups, low plasma Aβ42/40 was associated with more pronounced decline in composite cognitive score (adjusted between-group mean difference: -0.20, 95% CI, -0.34 to -0.07; P = .004) and decline in MMSE score (adjusted between-group mean difference: -0.59; 95% CI, -1.07 to -0.11; P = .02) during the follow-up period compared with the group with an Aβ42/40 ratio greater than 0.107. Conclusions and Relevance: In this study, low plasma Aβ42/40 was associated with more pronounced decline in cognitive function (measured by multiple outcomes) over time. Findings suggest that plasma Aβ42/40 may be used to identify people at risk of cognitive decline, being an alternative to more complex and expensive measures, such as positron emission tomography imaging or cerebrospinal fluid measurement.
Document Type: Article
Publication Stage: Final
Source: Scopus
“REV-ERBα mediates complement expression and diurnal regulation of microglial synaptic phagocytosis” (2020) eLife
REV-ERBα mediates complement expression and diurnal regulation of microglial synaptic phagocytosis
(2020) eLife, 9, .
Griffin, P.a , Sheehan, P.W.a , Dimitry, J.M.a , Guo, C.b , Kanan, M.F.a , Lee, J.a , Zhang, J.b , Musiek, E.S.a c
a Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, United States
b Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, United States
c Hope Center for Neurological Disorders, Washington University School of Medicine in St. Louis, St. Louis, United States
Abstract
The circadian clock regulates various aspects of brain health including microglial and astrocyte activation. Here, we report that deletion of the master clock protein BMAL1 in mice robustly increases expression of complement genes, including C4b and C3, in the hippocampus. BMAL1 regulates expression of the transcriptional repressor REV-ERBα, and deletion of REV-ERBα causes increased expression of C4b transcript in neurons and astrocytes as well as C3 protein primarily in astrocytes. REV-ERBα deletion increased microglial phagocytosis of synapses and synapse loss in the CA3 region of the hippocampus. Finally, we observed diurnal variation in the degree of microglial synaptic phagocytosis which was antiphase to REV-ERBα expression. This daily variation in microglial synaptic phagocytosis was abrogated by global REV-ERBα deletion, which caused persistently elevated synaptic phagocytosis. This work uncovers the BMAL1-REV-ERBα axis as a regulator of complement expression and synaptic phagocytosis in the brain, linking circadian proteins to synaptic regulation. © 2020, Griffin et al.
Author Keywords
circadian rhythm; complement; mouse; neuron-glia interactions; neuroscience; synaptic terminals
Document Type: Article
Publication Stage: Final
Source: Scopus
“Neurological and Neuropsychological Changes Associated with SARS-CoV-2 Infection: New Observations, New Mechanisms” (2020) Neuroscientist
Neurological and Neuropsychological Changes Associated with SARS-CoV-2 Infection: New Observations, New Mechanisms
(2020) Neuroscientist, .
Haidar, M.A.a , Jourdi, H.b , Haj Hassan, Z.c , Ashekyan, O.a , Fardoun, M.d , Wehbe, Z.d , Maaliki, D.e , Wehbe, M.f , Mondello, S.g , Abdelhady, S.h , Shahjouei, S.i , Bizri, M.j , Mechref, Y.k , Gold, M.S.l , Dbaibo, G.a m n , Zaraket, H.m o , Eid, A.H.e m , Kobeissy, F.a p
a Department of Biochemistry & Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
b Department of Biology, University of Balamand, Souk El Gharb, Aley, Lebanon
c Department of Animal Biology, Faculty of Science, Lebanese University, Beirut, Lebanon
d Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon
e Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
f Department of Internal Medicine, Basingstoke North Hampshire Hospital, Basingstoke, Hampshire, United Kingdom
g Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy
h Faculty of Medicine, Alexandria University, Alexandria, Egypt
i Neurology Department, Neuroscience Institute, Geisinger Health System, Danville, PA, United States
j Department of Psychiatry, American University of Beirut Medical Center, Beirut, Lebanon
k Texas Tech University, Lubbock, TX, United States
l Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
m Faculty of Medicine, Hariri School of Nursing, American University of Beirut, Beirut, Lebanon
n Center for Infectious Diseases Research, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
o Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
p Program for Neurotrauma, Neuroproteomics Biomarkers Research, Departments of Emergency Medicine, Psychiatry, Neuroscience and Chemistry, University of Florida, Gainesville, FL, United States
Abstract
SARS-CoV-2 infects cells through angiotensin-converting enzyme 2 (ACE2), a ubiquitous receptor that interacts with the virus’ surface S glycoprotein. Recent reports show that the virus affects the central nervous system (CNS) with symptoms and complications that include dizziness, altered consciousness, encephalitis, and even stroke. These can immerge as indirect immune effects due to increased cytokine production or via direct viral entry into brain tissue. The latter is possible through neuronal access via the olfactory bulb, hematogenous access through immune cells or directly across the blood-brain barrier (BBB), and through the brain’s circumventricular organs characterized by their extensive and highly permeable capillaries. Last, the COVID-19 pandemic increases stress, depression, and anxiety within infected individuals, those in isolation, and high-risk populations like children, the elderly, and health workers. This review surveys the recent updates of CNS manifestations post SARS-CoV-2 infection along with possible mechanisms that lead to them. © The Author(s) 2020.
Author Keywords
angiotensin; ARDS; autoantibodies; COVID-19; encephalitis; inflammation; neurodegeneration; pandemic; SARS; stroke; viral infection
Funding details
American University of BeirutAUB
Conseil National de la Recherche ScientifiqueCNRS-L
Document Type: Review
Publication Stage: Article in Press
Source: Scopus