“The impact of dopamine D2-like agonist/antagonist on (18F)VAT PET measurement of VAChT in the brain of nonhuman primates” (2020) European Journal of Pharmaceutical Sciences
The impact of dopamine D2-like agonist/antagonist on [18F]VAT PET measurement of VAChT in the brain of nonhuman primates
(2020) European Journal of Pharmaceutical Sciences, 143, art. no. 105152, .
Liu, H.a , Luo, Z.a , Gu, J.a , Su, Y.a , Flores, H.b , Parsons, S.M.c , Zhou, Y.a , Perlmutter, J.S.a b d , Tu, Z.a
a Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, United States
d Department of Neuroscience, Physical Therapy and Occupational Therapy, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Vesicular acetylcholine transporter (VAChT) is a promising target for a PET measure of cholinergic deficits which contribute to cognitive impairments. Dopamine D2-like agonists and antagonists are frequently used in the elderly and could alter cholinergic function and VAChT level. Therefore, pretreatment with dopamine D2-like drugs may interfere with PET measures using [18F]VAT, a specific VAChT radioligand. Herein, we investigated the impact of dopaminergic D2-like antagonist/agonist on VAChT level in the brain of macaques using [18F]VAT PET. PET imaging studies were carried out on macaques at baseline or pretreatment conditions. For pretreatment, animals were injected using a VAChT inhibitor (-)-vesamicol, a D2-like antagonist (-)-eticlopride, and a D2-like agonist (-)-quinpirole, separately. (-)-Vesamicol was injected at escalating doses of 0.025, 0.05, 0.125, 0.25 and 0.35 mg/kg; (-)-eticlopride was injected at escalating doses of 0.01, 0.10 and 0.30 mg/kg; (-)-quinpirole was injected at escalating doses of 0.20, 0.30, and 0.50 mg/kg. PET data showed [18F]VAT uptake declined in a dose-dependent manner by (-)-vesamicol pretreatment, demonstrating [18F]VAT uptake is sensitive to reflect the availability of VAChT binding sites. Furthermore, (-)-eticlopride increased [18F]VAT striatal uptake in a dose-dependent manner, while (-)-quinpirole decreased its uptake, suggesting striatal VAChT levels can be regulated by D2-like drug administration. Our findings confirmed [18F]VAT offers a reliable tool to in vivo assess the availability of VAChT binding sites. More importantly, PET with [18F]VAT successfully quantified the impact of dopaminergic D2-like drugs on striatal VAChT level, suggesting [18F]VAT has great potential for investigating the interaction between dopaminergic and cholinergic systems in vivo. © 2019 Elsevier B.V.
Author Keywords
Dopaminergic D2-like drugs; Nonhuman primates; PET; Vesicular acetylcholine transporter; [18F]VAT
Document Type: Article
Publication Stage: Final
Source: Scopus
“Utility of copy number variants in the classification of intracranial ependymoma” (2020) Cancer Genetics
Utility of copy number variants in the classification of intracranial ependymoma
(2020) Cancer Genetics, 240, pp. 66-72.
Evenson, M., Cai, C., Hucthagowder, V., McNulty, S., Neidich, J., Kulkarni, S., Dahiya, S.
Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, MO 63110, United States
Abstract
Ependymomas are neuroepithelial tumors that differentiate along the ependymal cell lineage, a lining of the ventricles of the brain and the central canal of the spinal cord. They are rare in adults, but account for around 9% of brain tumors in children, where they usually have an aggressive course. Efficient stratification could lead to improved care but remains a challenge even in the genomic era. Recent studies proposed a multivariate classification system based on tumor location, age, and broad genomic findings like global patterns of methylation and copy number variants (CNVs). This system shows improved prognostic utility, but is relatively impractical in the routine clinical setting because it necessitates multiple diagnostic tests. We analyzed 13 intracranial grade II and III ependymoma specimens on a DNA microarray to identify discrete CNVs that could support the existing classification. The loss of chr22 and the gain of 5p15.31 were common throughout our cohort (6 and 11 cases, respectively). Other CNVs correlated well with the previously proposed classification system. For example, gains of chr20 were unique to PF-EPN-B tumors of the posterior fossa and may differentiate them from PF-EPN-A. Given the ease of detecting CNVs using multiple, clinically validated methods, these CNVs should be further studied to confirm their diagnostic and prognostic utility, for incorporation into clinical testing algorithms. © 2019
Author Keywords
Anaplastic ependymoma; Brain tumors; Copy number variation; Ependymoma; Molecular classification; Whole genome
Document Type: Article
Publication Stage: Final
Source: Scopus
“Comments on the editor re: Shi, zumin, et al. ‘high chili intake and cognitive function among 4582 adults: An open cohort study over 15 years.’ nutrients 2019, 11(5), 1183″(2019) Nutrients
Comments on the editor re: Shi, zumin, et al. “high chili intake and cognitive function among 4582 adults: An open cohort study over 15 years.” nutrients 2019, 11(5), 1183
(2019) Nutrients, 11 (12), art. no. 2877, . Cited 1 time.
Wang, Y.a , Wu, D.b
a Department of Medicine, Washington University School of Medicine, St. Louis, MI 63110, United States
b Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, United Kingdom
Document Type: Note
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Modelling resilience in adolescence and adversity: a novel framework to inform research and practice” (2019) Translational Psychiatry
Modelling resilience in adolescence and adversity: a novel framework to inform research and practice
(2019) Translational Psychiatry, 9 (1), art. no. 316, .
Malhi, G.S.a b c , Das, P.a b c , Bell, E.a b c , Mattingly, G.d , Mannie, Z.a b c e
a Academic Department of Psychiatry, Northern Sydney Local Health District, St Leonards, NSW, Australia
b Sydney Medical School Northern, University of Sydney, Sydney, NSW, Australia
c CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia
d Washington University School of Medicine, St. Louis, MO 63110, United States
e NSW Health and Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia
Abstract
Recent conceptualisations of resilience have advanced the notion that it is a dynamic and multifaceted construct. However, its adaptive components, especially those forged by adversity, have not been fully realised, and its neurobiological and psychosocial underpinnings are yet to be meaningfully integrated. In part, this is because a developmental perspective is often neglected in the formulation of resilience. In this review, we consider the findings of resilience research, with a specific emphasis on the developmental period of adolescence. To bridge the gaps in our current understanding, we propose a model of resilience that is predicated on experiencing adversity. Specifically, our model provides a sophisticated insight into the components of resilience, which, together with intrinsic features, involves facilitation of, and skill acquisition via strengthening processes we term tempering and fortification. The model also points to the potential trajectories of adversity-driven resilience and forms the basis of a framework that allows for individual variance in resilience, and the identification of both neurobiological and psychosocial targets for prevention and therapeutic interventions. © 2019, The Author(s).
Document Type: Review
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Trial of SAGE-217 in Patients with Major Depressive Disorder. Reply” (2019) The New England Journal of Medicine
Trial of SAGE-217 in Patients with Major Depressive Disorder. Reply
(2019) The New England Journal of Medicine, 381 (22), p. 2179.
Gunduz-Bruce, H.a , Kanes, S.J.b , Zorumski, C.F.c
a Sage Therapeutics, MA, Cambridge
b Sage Therapeutics, MA, Cambridge
c Washington University School of Medicine, St. Louis, MO
Document Type: Letter
Publication Stage: Final
Source: Scopus
“Mouse methods and models for studies in hearing” (2019) Journal of the Acoustical Society of America
Mouse methods and models for studies in hearing
(2019) Journal of the Acoustical Society of America, 146 (5), pp. 3668-3680. Cited 5 times.
Ohlemiller, K.K.
Department of Otolaryngology, Central Institute for the Deaf, Washington University School of Medicine, Fay and Carl Simons Center for Hearing and Deafness, Saint Louis, MO 63110, United States
Abstract
Laboratory mice have become the dominant animal model for hearing research. The mouse cochlea operates according to standard “mammalian” principles, uses the same cochlear cell types, and exhibits the same types of injury as found in other mammals. The typical mouse lifespan is less than 3 years, yet the age-associated pathologies that may be found are quite similar to longer-lived mammals. All Schuknecht’s types of presbycusis have been identified in existing mouse lines, some favoring hair cell loss while others favor strial degeneration. Although noise exposure generally affects the mouse cochlea in a manner similar to other mammals, mice appear more prone to permanent alterations to hair cells or the organ of Corti than to hair cell loss. Therapeutic compounds may be applied systemically or locally through the tympanic membrane or onto (or through) the round window membrane. The thinness of the mouse cochlear capsule and annular ligament may promote drug entry from the middle ear, although an extremely active middle ear lining may quickly remove most drugs. Preclinical testing of any therapeutic will always require tests in multiple animal models. Mice constitute one model providing supporting evidence for any therapeutic, while genetically engineered mice can test hypotheses about mechanisms. © 2019 Acoustical Society of America.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Untangling the genomics of noise-induced hearing loss and tinnitus: Contributions of Mus musculus and Homo sapiens” (2019) Journal of the Acoustical Society of America
Untangling the genomics of noise-induced hearing loss and tinnitus: Contributions of Mus musculus and Homo sapiens
(2019) Journal of the Acoustical Society of America, 146 (5), pp. 4007-4019. Cited 2 times.
Clifford, R.E.a , Hertzano, R.b , Ohlemiller, K.K.c
a Division of Otolaryngology-Head and Neck Surgery, University of California School of Medicine, 9500 Gilman Drive, San diego, CA 92093, United States
b Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, James T. Frenkil Building, 16 South Eutaw Street, Baltimore, MD 21201, United States
c Washington University School of Medicine, Department of Otolaryngology, Central Institute for the Deaf, Washington University School of Medicine, Fay and Carl Simons Center for Hearing and Deafness, 660 South Euclid Avenue, Saint Louis, MO 63110, United States
Abstract
Acoustic trauma is a feature of the industrial age, in general, and mechanized warfare, in particular. Noise-induced hearing loss (NIHL) and tinnitus have been the number 1 and number 2 disabilities at U.S. Veterans hospitals since 2006. In a reversal of original protocols to identify candidate genes associated with monogenic deafness disorders, unbiased genome-wide association studies now direct animal experiments in order to explore genetic variants common in Homo sapiens. However, even these approaches must utilize animal studies for validation of function and understanding of mechanisms. Animal research currently focuses on genetic expression profiles since the majority of variants occur in non-coding regions, implying regulatory divergences. Moving forward, it will be important in both human and animal research to define the phenotypes of hearing loss and tinnitus, as well as exposure parameters, in order to extricate genes related to acoustic trauma versus those related to aging. It has become clear that common disorders like acoustic trauma are influenced by large numbers of genes, each with small effects, which cumulatively lead to susceptibility to a disorder. A polygenic risk score, which aggregates these small effect sizes of multiple genes, may offer a more accurate description of risk for NIHL and/or tinnitus. © 2019 Acoustical Society of America.
Document Type: Article
Publication Stage: Final
Source: Scopus
“In support of selective dorsal rhizotomy in cerebral palsy: the strength of clinical experience” (2019) Developmental Medicine and Child Neurology
In support of selective dorsal rhizotomy in cerebral palsy: the strength of clinical experience
(2019) Developmental Medicine and Child Neurology, .
Park, T.S.
Department of Neurosurgery, St. Louis Children’s Hospital, Washington University in St. Louis, St. Louis, MO, United States
Document Type: Letter
Publication Stage: Article in Press
Source: Scopus
“Parent–child neural synchrony: a novel approach to elucidating dyadic correlates of preschool irritability” (2019) Journal of Child Psychology and Psychiatry and Allied Disciplines
Parent–child neural synchrony: a novel approach to elucidating dyadic correlates of preschool irritability
(2019) Journal of Child Psychology and Psychiatry and Allied Disciplines, .
Quiñones-Camacho, L.E.a , Fishburn, F.A.b , Camacho, M.C.c , Hlutkowsky, C.O.b , Huppert, T.J.d , Wakschlag, L.S.e f , Perlman, S.B.a c
a Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
b Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States
c Department of Neuroscience, Washington University in St. Louis, St. Louis, MO, United States
d Department of Radiology, University of Pittsburgh, Pittsburgh, PA, United States
e Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
f Institute for Innovations in Developmental Sciences, Northwestern University, Chicago, IL, United States
Abstract
Background: Research to date has largely conceptualized irritability in terms of intraindividual differences. However, the role of interpersonal dyadic processes has received little consideration. Nevertheless, difficulties in how parent–child dyads synchronize during interactions may be an important correlate of irritably in early childhood. Innovations in developmentally sensitive neuroimaging methods now enable the use of measures of neural synchrony to quantify synchronous responses in parent–child dyads and can help clarify the neural underpinnings of these difficulties. We introduce the Disruptive Behavior Diagnostic Observation Schedule: Biological Synchrony (DB-DOS:BioSync) as a paradigm for exploring parent–child neural synchrony as a potential biological mechanism for interpersonal difficulties in preschool psychopathology. Methods: Using functional near-infrared spectroscopy (fNIRS) 4- to 5-year-olds (N = 116) and their mothers completed the DB-DOS:BioSync while assessing neural synchrony during mild frustration and recovery. Child irritability was measured using a latent irritability factor that was calculated from four developmentally sensitive indicators. Results: Both the mild frustration and the recovery contexts resulted in neural synchrony. However, less neural synchrony during the recovery context only was associated with more child irritability. Conclusions: Our results suggest that recovering after a frustrating period might be particularly challenging for children high in irritability and offer support for the use of the DB-DOS:BioSync task to elucidate interpersonal neural mechanisms of developmental psychopathology. © 2019 Association for Child and Adolescent Mental Health
Author Keywords
irritability; Neural synchrony; parent–child synchrony; prefrontal cortex; recovery
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Adrenergic chromaffin cells are adrenergic even in the absence of epinephrine” (2019) Journal of Neurochemistry
Adrenergic chromaffin cells are adrenergic even in the absence of epinephrine
(2019) Journal of Neurochemistry, .
González-Santana, A.a , Castañeyra, L.a g , Baz-Dávila, R.a , Estévez-Herrera, J.a , Domínguez, N.b , Méndez, I.c , Padín, L.F.c d , Castañeyra, A.e , Machado, J.-D.a , Ebert, S.N.f , Borges, R.a
a Unidad de Farmacología, Facultad de Medicina, Universidad de la Laguna, Tenerife, Spain
b INTEGRARE, Généthon, Inserm, Univ Evry, Université Paris-Saclay, Evry, France
c Instituto Teófilo Hernando, Universidad Autónoma de Madrid, Madrid, Spain
d Departamento Ciencias Médicas (Farmacología), Facultad de Medicina, Universidad de Castilla-La Mancha, Ciudad Real, Spain
e Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad de La Laguna, Tenerife, Spain
f Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, United States
g Department of Neurosurgery, School of Medicine, Washington University in Saint Louis, St. Louis, MO, United States
Abstract
Adrenal chromaffin cells release epinephrine (EPI) and norepinephrine (NE) into the bloodstream as part of the homeostatic response to situations like stress. Here we utilized EPI-deficient mice generated by knocking out (KO) the phenylethanolamine N-methyltransferase (Pnmt) gene. These Pnmt-KO mice were bred to homozygosis but displayed no major phenotype. The lack of EPI was partially compensated by an increase in NE, suggesting that EPI storage was optimized in adrenergic cells. Electron microscopy showed that despite the lack of EPI, chromaffin granules retain their shape and general appearance. This indicate that granules from adrenergic or noradrenergic cells preserve their characteristics even though they contain only NE. Acute insulin injection largely reduced the EPI content in wild-type animals, with a minimal reduction in NE, whereas there was only a partial reduction in NE content in Pnmt-KO mice. The analysis of exocytosis by amperometry revealed a reduction in the quantum size (−30%) and Imax (−21%) of granules in KO cells relative to the wild-type granules, indicating a lower affinity of NE for the granule matrix of adrenergic cells. As amperometry cannot distinguish between adrenergic or noradrenergic cells, it would suggest even a larger reduction in the affinity for the matrix. Therefore, our results demonstrate that adrenergic cells retain their structural characteristics despite the almost complete absence of EPI. Furthermore, the chromaffin granule matrix from adrenergic cells is optimized to accumulate EPI, with NE being a poor substitute. Open science badges: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. (Figure presented.). © 2019 International Society for Neurochemistry
Author Keywords
adrenal; chromaffin; epinephrine; exocytosis; norepinephrine; secretion
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Transcriptional profiling of medulloblastoma with extensive nodularity (MBEN) reveals two clinically relevant tumor subsets with VSNL1 as potent prognostic marker” (2019) Acta Neuropathologica
Transcriptional profiling of medulloblastoma with extensive nodularity (MBEN) reveals two clinically relevant tumor subsets with VSNL1 as potent prognostic marker
(2019) Acta Neuropathologica, .
Korshunov, A.a b c , Okonechnikov, K.c d , Sahm, F.a b c , Ryzhova, M.e , Stichel, D.a b , Schrimpf, D.a b , Ghasemi, D.R.c d , Pajtler, K.W.c d , Antonelli, M.f , Donofrio, V.g , Mastronuzzi, A.h , Rossi, S.i , Camassei, F.D.i , Buccoliero, A.M.j , Haberler, C.k , Slavc, I.l , Dahiya, S.m , Casalini, B.a b , Sievers, P.a b , Meyer, J.a b , Kumirova, E.n , Zheludkova, O.o , Golanov, A.p , Jones, D.T.W.c q , Pfister, S.M.c d r , Kool, M.c d s , von Deimling, A.a b c
a Clinical Cooperation Unit Neuropathology (B300), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, 69120, Germany
b Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany
c Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
d Division of Pediatric Neurooncology (B062), German Cancer Research Center (DKFZ), Heidelberg, Germany
e Department of Neuropathology, NN Burdenko Neurosurgical Institute, Moscow, Russian Federation
f Department of radiological oncological and anatomic pathology sciences, Policlinico Umberto I Università Sapienza, Rome, Italy
g Pathology Unit, Ospedale Santobono-Pausilipon, Naples, Italy
h Department of Onco-Hematology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital, Rome, Italy
i Department of Laboratories, Pathology Unit, Bambino Gesù Children’s Hospital, Rome, Italy
j Pathology Unit, A. Meyer University Children’s Hospital, Florence, Italy
k Institute of Neurology, Medical University of Vienna, Vienna, Austria
l Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
m Division of Neuropathology, Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, United States
n Department of Neuro-Oncology, Dmitry Rogachev National Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
o Department of Neuro-Oncology, Russian Scientific Center of Radiology, Moscow, Russian Federation
p Department of Neuroradiology, NN Burdenko Neurosurgical Institute, Moscow, Russian Federation
q Pediatric Glioma Research Group (B360), German Cancer Research Center (DKFZ), Heidelberg, Germany
r Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany
s Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands
Abstract
Medulloblastoma with extensive nodularity (MBEN) is one of the few central nervous system (CNS) tumor entities occurring in infants which is traditionally associated with good to excellent prognosis. Some MBEN, however, have been reported with an unfavorable clinical course. We performed an integrated DNA/RNA-based molecular analysis of a multi-institutional MBEN cohort (n = 41) to identify molecular events which might be responsible for variability in patients’ clinical outcomes. RNA sequencing analysis of this MBEN cohort disclosed two clear transcriptome clusters (TCL) of these CNS tumors: “TCL1 MBEN” and “TCL2 MBEN” which were associated with various gene expression signatures, mutational landscapes and, importantly, prognosis. Thus, the clinically unfavorable “TCL1 MBEN” subset revealed transcriptome signatures composed of cancer-associated signaling pathways and disclosed a high frequency of clinically relevant germline PTCH1/SUFU alterations. In contrast, gene expression profiles of tumors from the clinically favorable “TCL2 MBEN” subgroup were associated with activation of various neurometabolic and neurotransmission signaling pathways, and germline SHH-pathway gene mutations were extremely rare in this transcriptome cluster. “TCL2 MBEN” also revealed strong and ubiquitous expression of VSNL1 (visinin-like protein 1) both at the mRNA and protein level, which was correlated with a favorable clinical course. Thus, combining mutational and epigenetic profiling with transcriptome analysis including VSNL1 immunohistochemistry, MBEN patients could be stratified into clinical risk groups of potential value for subsequent treatment planning. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
Author Keywords
MBEN; Medulloblastoma; Prognosis; Transcriptome; VSNL1
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Effect of workflow metrics on clinical outcomes of low diffusion-weighted imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) patients subjected to mechanical thrombectomy” (2019) Journal of NeuroInterventional Surgery
Effect of workflow metrics on clinical outcomes of low diffusion-weighted imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) patients subjected to mechanical thrombectomy
(2019) Journal of NeuroInterventional Surgery, .
Panni, P.a , Michelozzi, C.b , Richard, S.c , Marnat, G.d , Blanc, R.e , Consoli, A.f , Mazighi, M.g , Piotin, M.g , Dargazanli, C.h , Arquizane, C.i , Sibon, I.j , Anxionnat, R.k , Hossu, G.l , Bourcier, R.m , Anadani, M.n o , Lapergue, B.p , Gory, B.k
a Interventional Neuroradiology and Neurosurgery, Vita-salute San Raffaele University Hospital, Vita-salute San Raffaele University, Milano, 20132, Italy
b Interventional Neuroradiology, Vita-Salute San Raffaele University Hospital, Vita-Salute San Raffaele University, Milano, Italy
c Neurology Stroke Unit, University Hospital Centre Nancy, Nancy, France
d Interventional and Diagnostic Neuroradiology, Bordeaux University Hospital, Bordeaux, France
e Departement of Interventional Neuroradiology, Fondation Rothschild Hospital, Paris, France
f Interventional Neuroradiologie, Hopital Foch, Ile-de-France, Suresnes, France
g Departement of Interventional Neuroradiology, Fondation Rothschild Hospital, paris, France
h Department of Neuroradiology, University Hospital Centre Montpellier Occitanie, Montpellier, France
i Department of Neurology, University Hospital Centre Montpellier, Occitanie, Montpellier, France
j Bordeaux 1 University, Aquitaine, Talence, France
k Department of Diagnostic and Interventional Neuroradiology, CHRU Nancy, Lorraine, Nancy, France
l Université de Lorraine, Faculté de Médecine, Lorraine, Vandœuvre-lès-Nancy, France
m Department of Neuroradiology, Interventional Neuroradiology, University Hospital Nantes, Nantes, France
n Washington University School of Medicine in Saint Louis, Saint Louis, MO, United States
o Department Neurology, Medical University of South Carolina, College of Medicine, Charleston, SC, United States
p Department of Neurology, Foch Hospital, Paris, France
Abstract
Background: Although accumulating evidence has demonstrated the benefit of mechanical thrombectomy (MT) in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS), it is still unclear how workflow metrics impact the clinical outcomes of this subgroup of patients. Methods: Patients with acute stroke and diffusion-weighted imaging (DWI) ASPECTS ≤5 at baseline, who underwent MT within 6 hours of symptoms onset, were included from a prospectively maintained national multicentric registry between January 1, 2012 to August 31, 2017. The degree of disability was assessed by the modified Rankin Scale (mRS) at 90 days. The primary outcome was functional independence defined as mRS 0 to 2 at 90 days. Results: The study included 291 patients with baseline DWI-ASPECTS ≤5. Good outcome was achieved in 82 (28.2%) patients, and 104 (35.7%) patients died within 90 days. Successful reperfusion (modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3) rate was 75.3%, and median onset to recanalization (OTR) time was 2 268min. Among time-related variables, OTR emerged as the strongest predictor of primary outcome (adjusted OR for every 60 min 0.59, 95% CI 0.44 to 0.77; p<0.001). mTICI 2c-3 independently predicted a good outcome (adjusted OR 1.91, 95% CI 1.004 to 3.6; p=0.049) along with age and baseline DWI-ASPECTS. Recanalization status failed to significantly impact outcome in the DWI-ASPECTS 0-3 subpopulation. Conclusions: Near complete reperfusion (mTICI 2c-3) and OTR are the strongest modifiable outcome predictors in patients with DWI-ASPECTS ≤5 treated with MT. © Author(s) (or their employer(s)) 2019.
Author Keywords
brain; intervention; MRI; stroke
Document Type: Article
Publication Stage: Article in Press
Source: Scopus