Diagnosis and classification of blepharospasm: Recommendations based on empirical evidence
(2022) Journal of the Neurological Sciences, 439, art. no. 120319, .
Kilic-Berkmen, G.a , Defazio, G.b , Hallett, M.c , Berardelli, A.d e , Ferrazzano, G.d , Belvisi, D.d e , Klein, C.f , Bäumer, T.g , Weissbach, A.f g , Perlmutter, J.S.h , Feuerstein, J.i , Jinnah, H.A.a j , for the Dystonia Coalition Investigatorsk
a Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
b Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
c Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, MD, United States
d Department of Human Neuroscience, Sapienza University of Rome, Viale dell’Università 30, Rome, 00185, Italy
e IRCCS NEUROMED, Via Atinense 18, Pozzilli, 86077, Italy
f Institute of Neurogenetics and Department of Neurology, University of Luebeck, University Hospital of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
g Institute of System Motor Science, University of Lübeck, Ratzeburger Allee 160, Lübeck, Germany
h Department of Neurology, Radiology, Neuroscience, Physical Therapy and Occupational Therapy, Washington University School of Medicine, St Louis, MO, United States
i Department of Neurology, University of Colorado, Aurora, CO, United States
j Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, United States
Abstract
Background: Blepharospasm is one of the most common subtypes of dystonia, and often spreads to other body regions. Despite published guidelines, the approach to diagnosis and classification of affected body regions varies among clinicians. Objective: To delineate the clinical features used by movement disorder specialists in the diagnosis and classification of blepharospasm according to body regions affected, and to develop recommendations for a more consistent approach. Methods: Cross-sectional data for subjects diagnosed with all types of isolated dystonia were acquired from the Dystonia Coalition, an international, multicenter collaborative research network. Data were evaluated to determine how examinations recorded by movement disorder specialists were used to classify blepharospasm as focal, segmental, or multifocal. Results: Among all 3222 participants with isolated dystonia, 210 (6.5%) had a diagnosis of focal blepharospasm. Among these 210 participants, 34 (16.2%) had dystonia outside of upper face region. Factors such as dystonia severity across different body regions and number of body regions affected influenced the classification of blepharospasm as focal, segmental, or multifocal. Conclusions: Although focal blepharospasm is the second most common type of dystonia, a high percentage of individuals given this diagnosis had dystonia outside of the eye/upper face region. These findings are not consistent with existing guidelines for the diagnosis and classification of focal blepharospasm, and point to the need for more specific guidelines for more consistent application of existing recommendations for diagnosis and classification. © 2022
Author Keywords
Blepharospasm; Craniofacial dystonia; Meige syndrome
Funding details
National Institutes of HealthNIH
National Institute on AgingNIANS075321
National Institute of Neurological Disorders and StrokeNINDS
Dystonia Medical Research FoundationDMRF
California Department of Fish and GameDFGWE5919/2–1
National Center for Advancing Translational SciencesNCATS
American Parkinson Disease AssociationAPDA
Foundation for Barnes-Jewish HospitalFBJH
Allergan
International Parkinson and Movement Disorder SocietyMDS
Benign Essential Blepharospasm Research FoundationBEBRF
Tourette Association of AmericaTAA
National Spasmodic Dysphonia AssociationNSDA
Acorda Therapeutics
Dystonia CoalitionNS065701, NS116025, TR001456
Government of South Australia
RevanceRVNC
Paula and Rodger Riney Foundation
Deutsche ForschungsgemeinschaftDFGFG 2698, SFB 936
Else Kröner-Fresenius-StiftungEKFS2018_A55
Ipsen
Document Type: Article
Publication Stage: Final
Source: Scopus
Delay of gratification dissociates cognitive control and valuation brain regions in healthy young adults
(2022) Neuropsychologia, 173, art. no. 108303, .
Lamichhane, B.a b , Di Rosa, E.c , Braver, T.S.d
a Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, United States
b Center for Health Sciences, Oklahoma State University, 1013 E 66th Pl, Tulsa, OK 74136, United States
c Department of General Psychology, University of Padova, Padova, Italy
d Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, United States
Abstract
Delay of gratification (DofG) refers to an inter-temporal choice phenomenon that is of great interest in many domains, including animal learning, cognitive development, economic decision-making, and executive control. Yet experimental tools for investigating DofG in human adults are almost non-existent, and as a consequence, very little is known regarding the brain basis of core DofG behaviors. Here, we utilize a novel DofG paradigm, adapted for use in neuroimaging contexts, to examine event-related changes in neural activity as healthy young adult participants made repeated choices to continue waiting for a delayed reward, rather than take an immediately available one of lesser value. On DofG trials, choose-to-wait events were associated with increased activation in fronto-parietal and cingulo-opercular regions associated with cognitive control. Activity in the right lateral prefrontal cortex (PFC) was also associated with individual variability in task performance and strategy. Fronto-parietal activity was clearly dissociable from that observed in ventromedial PFC, as this latter region exhibited a ramping-up pattern of activity during the waiting period prior to reward delivery. Ventromedial PFC ramping activity dynamics were further selective to DofG trials associated with increased future reward rate, consistent with the involvement of this region in subjective reward valuation that incorporates higher-order task structure. These results provide important initial validation of this experimental paradigm as a useful tool for investigating and isolating unique DofG neural mechanisms, which can now be utilized to study a wide-variety of populations and task factors. © 2022 The Authors
Author Keywords
Decision making; Delay discounting; fMRI; Impulsivity; Motivation; Reward; Self-control
Funding details
National Institutes of HealthNIH
National Institute on AgingNIAR01AG043461, R21AG058206, R21AG067295
Horizon 2020
Document Type: Article
Publication Stage: Final
Source: Scopus
Characterisation of the genetic relationship between the domains of sleep and circadian-related behaviours with substance use phenotypes
(2022) Addiction Biology, 27 (4), art. no. e13184, .
Hatoum, A.S.a , Winiger, E.A.b , Morrison, C.L.c d , Johnson, E.C.a , Agrawal, A.a
a Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, United States
b Department of Psychiatry, University of Colorado School of Medicine, Denver, CO, United States
c Institute for Behavioral Genetics, University of Colorado, Boulder, CO, United States
d Department of Psychology and Neuroscience, University of Colorado, Boulder, CO, United States
Abstract
Sleep problems and substance use frequently co-occur. While substance use can result in specific sleep deficits, genetic pleiotropy could explain part of the relationship between sleep and substance use and use disorders. Here we use the largest publicly available genome-wide summary statistics of substance use behaviours (N = 79,729–632,802) and sleep/activity phenotypes to date (N = 85,502–449,734) to (1) assess the genetic overlap between substance use behaviours and both sleep and circadian-related activity measures, (2) estimate clusters from genetic correlations and (3) test processes of causality versus genetic pleiotropy. We found 31 genetic correlations between substance use and sleep/activity after Bonferroni correction. These patterns of overlap were represented by two genetic clusters: (1) tobacco use severity (age of first regular tobacco use and smoking cessation) and sleep health (sleep duration, sleep efficiency and chronotype) and (2) substance consumption/problematic use (drinks per day and cigarettes per day, cannabis use disorder, opioid use disorder and problematic alcohol use) and sleep problems (insomnia, self-reported short sleep duration, increased number of sleep episodes, increased sleep duration variability and diurnal inactivity) and measures of circadian-related activity (L5, M10 and sleep midpoint). Latent causal variable analyses determined that horizontal pleiotropy (rather than genetic causality) underlies a majority of the associations between substance use and sleep/circadian related measures, except one plausible genetically causal relationship for opioid use disorder on self-reported long sleep duration. Results show that shared genetics are likely a mechanism that is at least partly responsible for the overlap between sleep and substance use traits. © 2022 Society for the Study of Addiction.
Author Keywords
genetic correlations; sleep; substance use
Funding details
DA054869, K01DA051759, K02DA032573
National Institute of Mental HealthNIMHMH016880, T32 MH015442
National Institute on Drug AbuseNIDADA017637, T32DA007261-17
Document Type: Article
Publication Stage: Final
Source: Scopus
Pitch Accuracy of Vocal Singing in Deaf Children With Bimodal Hearing and Bilateral Cochlear Implants
(2022) Ear and Hearing, 43 (4), pp. 1336-1346.
Xu, L.a , Yang, J.b , Hahn, E.a , Uchanski, R.c , Davidson, L.c
a Communication Sciences and Disorders, Ohio UniversityOH, United States
b Communication Sciences and Disorders, University of Wisconsin-MilwaukeeWI, United States
c Department of Otolaryngology, Washington University in St. Louis School of MedicineMO, United States
Abstract
OBJECTIVES: The purpose of the present study was to investigate the pitch accuracy of vocal singing in children with severe to profound hearing loss who use bilateral cochlear implants (CIs) or bimodal devices [CI at one ear and hearing aid (HA) at the other] in comparison to similarly-aged children with normal-hearing (NH). DESIGN: The participants included four groups: (1) 26 children with NH, (2) 13 children with bimodal devices, (3) 31 children with bilateral CIs that were implanted sequentially, and (4) 10 children with bilateral CIs that were implanted simultaneously. All participants were aged between 7 and 11 years old. Each participant was recorded singing a self-chosen song that was familiar to him or her. The fundamental frequencies (F0) of individual sung notes were extracted and normalized to facilitate cross-subject comparisons. Pitch accuracy was quantified using four pitch-based metrics calculated with reference to the target music notes: mean note deviation, contour direction, mean interval deviation, and F0 variance ratio. A one-way ANOVA was used to compare listener-group difference on each pitch metric. A principal component analysis showed that the mean note deviation best accounted for pitch accuracy in vocal singing. A regression analysis examined potential predictors of CI children’s singing proficiency using mean note deviation as the dependent variable and demographic and audiological factors as independent variables. RESULTS: The results revealed significantly poorer performance on all four pitch-based metrics in the three groups of children with CIs in comparison to children with NH. No significant differences were found among the three CI groups. Among the children with CIs, variability in the vocal singing proficiency was large. Within the group of 13 bimodal users, the mean note deviation was significantly correlated with their unaided pure-tone average thresholds (r = 0.582, p = 0.037). The regression analysis for all children with CIs, however, revealed no significant demographic or audiological predictor for their vocal singing performance. CONCLUSION: Vocal singing performance in children with bilateral CIs or bimodal devices is not significantly different from each other on a group level. Compared to children with NH, the pediatric bimodal and bilateral CI users, in general, demonstrated significant deficits in vocal singing ability. Demographic and audiological factors, known from previous studies to be associated with good speech and language development in prelingually-deafened children with CIs, were not associated with singing accuracy for these children. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Document Type: Article
Publication Stage: Final
Source: Scopus
Neurointerventional management of cerebrovascular trauma
(2022) Journal of Neurointerventional Surgery, 14 (7), pp. 718-722.
Lauzier, D.C.a , Chatterjee, A.R.a b c , Kansagra, A.P.a b c
a Mallinckrodt Institute of Radiology, Washington University School of Medicine in Saint Louis, St Louis, MO, United States
b Department of Neurological Surgery, Washington University School of Medicine in Saint Louis, Saint Louis, Missouri, USA
c Department of Neurology, Washington University School of Medicine in Saint Louis, Saint Louis, Missouri, USA
Abstract
Traumatic cerebrovascular injuries following blunt or penetrating trauma are common and carry a high risk of permanent disability or death. Proper screening, diagnosis, and treatment of these lesions is essential to improve patient outcomes. Advances in imaging continue to improve the accuracy of non-invasive diagnosis of these injuries while new clinical data provide better evidence for optimal management, whether medical or invasive. Here, we review screening, diagnosis, and treatment of traumatic cerebrovascular injuries. © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.
Author Keywords
angiography; dissection; intervention; trauma
Document Type: Review
Publication Stage: Final
Source: Scopus
Cholesterol and matrisome pathways dysregulated in astrocytes and microglia
(2022) Cell, 185 (13), pp. 2213-2233.e25. Cited 1 time.
TCW, J.a b c d , Qian, L.a b c d , Pipalia, N.H.e , Chao, M.J.b c d m , Liang, S.A.f , Shi, Y.g h , Jain, B.R.f , Bertelsen, S.E.c d , Kapoor, M.b c d n , Marcora, E.b c d , Sikora, E.c d , Andrews, E.J.i j , Martini, A.C.i j , Karch, C.M.h k , Head, E.f i j , Holtzman, D.M.g h , Zhang, B.b d l , Wang, M.b l , Maxfield, F.R.e , Poon, W.W.f o , Goate, A.M.b c d
a Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, United States
b Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
c Nash Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
d Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
e Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, United States
f Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, United States
g Department of Neurology, Washington University School of Medicine, St. Louis, MO 63108, United States
h Hope Center for Neurological Disorders, Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MO 63108, United States
i Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA 92697, United States
j Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA 92697, United States
k Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63108, United States
l Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
m Sanofi US, Cambridge, MA 02141, United States
n Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, United States
o NeuCyte, Inc., Mountain View, CA 94043, United States
Abstract
The impact of apolipoprotein E ε4 (APOE4), the strongest genetic risk factor for Alzheimer’s disease (AD), on human brain cellular function remains unclear. Here, we investigated the effects of APOE4 on brain cell types derived from population and isogenic human induced pluripotent stem cells, post-mortem brain, and APOE targeted replacement mice. Population and isogenic models demonstrate that APOE4 local haplotype, rather than a single risk allele, contributes to risk. Global transcriptomic analyses reveal human-specific, APOE4-driven lipid metabolic dysregulation in astrocytes and microglia. APOE4 enhances de novo cholesterol synthesis despite elevated intracellular cholesterol due to lysosomal cholesterol sequestration in astrocytes. Further, matrisome dysregulation is associated with upregulated chemotaxis, glial activation, and lipid biosynthesis in astrocytes co-cultured with neurons, which recapitulates altered astrocyte matrisome signaling in human brain. Thus, APOE4 initiates glia-specific cell and non-cell autonomous dysregulation that may contribute to increased AD risk. © 2022 Elsevier Inc.
Author Keywords
Alzheimer; APOE; astrocytes; cholesterol; genetic heterogeneity; haplotypes; inflammation; iPSC disease modeling; matrisome; microglia
Funding details
AOC-207373
WO/2018/160496
K01AG062683
P30AG066444
National Institutes of HealthNIH1S10OD021718-01, OD 1S10OD010794-01
National Institute on AgingNIAU01AG058635, U19AG069701
National Heart, Lung, and Blood InstituteNHLBIR01HL093324
National Institute of Neurological Disorders and StrokeNINDSRF1AG047644, RF1NS090934
National Center for Research ResourcesNCRR1S10RR025496-01
New York Stem Cell FoundationNYSCF
Pfizer
GlaxoSmithKlineGSK
Biogen
AbbVie
JPB FoundationJPBFP50AG016573
Cure Alzheimer’s FundCAFRF1AG054014, RF1AG057440, RF1AG074010, U01AG046170
University of California, IrvineUCIP30AG066519
Eisai
Document Type: Article
Publication Stage: Final
Source: Scopus
Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive
(2022) Malaria Journal, 21 (1), p. 196.
O’Brien, N.F.a , Fonseca, Y.b , Johnson, H.C.b , Postels, D.c , Birbeck, G.L.d e , Chimalizeni, Y.f , Seydel, K.B.g , Bernard Gushu, M.h , Phiri, T.h , June, S.h , Chetcuti, K.f , Vidal, L.i , Goyal, M.S.j , Taylor, T.E.g
a Department of Pediatrics, Division of Critical Care Medicine, Nationwide Children’s Hospital, The Ohio State University, 700 Children’s Drive, Columbus, OH, 43502, USA. Nicole.obrien@nationwidechildrens.org
b Department of Pediatrics, Division of Critical Care Medicine, Nationwide Children’s Hospital, The Ohio State University, 700 Children’s Drive, Columbus, OH, 43502, USA
c Department of Neurology, George Washington University/Children’s National Medical Center, DCWA, United States
d Department of Neurology, University of Rochester, Rochester, NY, USA
e University Teaching Hospitals Children’s HospitalLusaka, Zambia
f Department of Pediatrics and Child Health, Kamuzu University of Health Sciences, Blantyre 3, Malawi
g Dept of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, MI, East Lansing, 48824, United States
h Queen Elizabeth Central Hospital, Blantyre Malaria Project, Private Bag 360, Blantyre 3, Malawi
i Department of Radiology, Division of Neuroradiology, Children’s Hospital of Philadelphia, University of Pennsylvania, PA, Philadelphia, 19104, United States
j Washington University School of Medicine, St. Louis, MO, USA
Abstract
BACKGROUND: Cerebral malaria (CM) results in significant paediatric death and neurodisability in sub-Saharan Africa. Several different alterations to typical Transcranial Doppler Ultrasound (TCD) flow velocities and waveforms in CM have been described, but mechanistic contributors to these abnormalities are unknown. If identified, targeted, TCD-guided adjunctive therapy in CM may improve outcomes. METHODS: This was a prospective, observational study of children 6 months to 12 years with CM in Blantyre, Malawi recruited between January 2018 and June 2021. Medical history, physical examination, laboratory analysis, electroencephalogram, and magnetic resonance imaging were undertaken on presentation. Admission TCD results determined phenotypic grouping following a priori definitions. Evaluation of the relationship between haemodynamic, metabolic, or intracranial perturbations that lead to these observed phenotypes in other diseases was undertaken. Neurological outcomes at hospital discharge were evaluated using the Paediatric Cerebral Performance Categorization (PCPC) score. RESULTS: One hundred seventy-four patients were enrolled. Seven (4%) had a normal TCD examination, 57 (33%) met criteria for hyperaemia, 50 (29%) for low flow, 14 (8%) for microvascular obstruction, 11 (6%) for vasospasm, and 35 (20%) for isolated posterior circulation high flow. A lower cardiac index (CI) and higher systemic vascular resistive index (SVRI) were present in those with low flow than other groups (p < 0.003), though these values are normal for age (CI 4.4 [3.7,5] l/min/m2, SVRI 1552 [1197,1961] dscm-5m2). Other parameters were largely not significantly different between phenotypes. Overall, 118 children (68%) had a good neurological outcome. Twenty-three (13%) died, and 33 (19%) had neurological deficits. Outcomes were best for participants with hyperaemia and isolated posterior high flow (PCPC 1-2 in 77 and 89% respectively). Participants with low flow had the least likelihood of a good outcome (PCPC 1-2 in 42%) (p < 0.001). Cerebral autoregulation was significantly better in children with good outcome (transient hyperemic response ratio (THRR) 1.12 [1.04,1.2]) compared to a poor outcome (THRR 1.05 [0.98,1.02], p = 0.05). CONCLUSIONS: Common pathophysiological mechanisms leading to TCD phenotypes in non-malarial illness are not causative in children with CM. Alternative mechanistic contributors, including mechanical factors of the cerebrovasculature and biologically active regulators of vascular tone should be explored. © 2022. The Author(s).
Author Keywords
Cerebral blood flow; Cerebral malaria; Paediatric; Transcranial Doppler Ultrasound
Document Type: Article
Publication Stage: Final
Source: Scopus
Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis: An international consensus recommendation
(2022) Genetics in Medicine, .
Plotkin, S.R.a , Messiaen, L.b , Legius, E.c , Pancza, P.d , Avery, R.A.e , Blakeley, J.O.f , Babovic-Vuksanovic, D.g , Ferner, R.h , Fisher, M.J.i , Friedman, J.M.j , Giovannini, M.k , Gutmann, D.H.l , Hanemann, C.O.m , Kalamarides, M.n , Kehrer-Sawatzki, H.o , Korf, B.R.b , Mautner, V.-F.p , MacCollin, M.q , Papi, L.r , Rauen, K.A.s , Riccardi, V.t , Schorry, E.u , Smith, M.J.v , Stemmer-Rachamimov, A.w , Stevenson, D.A.x , Ullrich, N.J.y , Viskochil, D.z , Wimmer, K.aa , Yohay, K.ab , Huson, S.M.ac , Wolkenstein, P.ad , Evans, D.G.v , International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC)ae
a Department of Neurology and Cancer Center, Massachusetts General Hospital, Boston, MA
b Department of Genetics, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL
c Department of Human Genetics, Member of ERN GENTURIS, KU Leuven and University Hospital, Leuven, Belgium
d Children’s Tumor Foundation, New York, NY
e Division of Ophthalmology, The Children’s Hospital of Philadelphia, Philadelphia, PA
f Comprehensive Neurofibromatosis Center, Johns Hopkins Medicine, The Johns Hopkins Hospital, Baltimore, MD
g Department of Clinical Genomics, Mayo Clinic College of Medicine and Science, Rochester, MN
h Neurology, Guy’s and St. Thomas’ Hospital and NHS Trust, London, United Kingdom
i Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, PA
j Department of Medical Genetics, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada
k Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA and Jonsson Comprehensive Cancer Center (JCCC), University of California, Los Angeles, CA
l Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO
m Institute of Translational and Stratified Medicine, Peninsula Medical School, University of Plymouth, Plymouth, United Kingdom
n Department of Neurosurgery, Hospital Pitie-Salpetriere, Sorbonne Université, Paris, France
o Institute of Human Genetics, University of Ulm, Ulm, Germany
p Department of Neurology, University Hospital of Hamburg-Eppendorf, Hamburg, Germany
q Pediatric Neurology, Bend, OR
r The Department of Experimental and Clinical, Medical Genetics Unit, Biomedical Sciences “Mario Serio,” University of Florence, Florence, Italy
s Department of Pediatrics, University of California Davis, Sacramento, CA
t The Neurofibromatosis Institute, La Crescenta, CA, United States
u Medical Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
v Manchester Centre for Genomic Medicine, St Mary’s Hospital, Manchester Academic Health Sciences Centre (MAHSC), Member of ERN GENTURIS, Division of Evolution, Infection and Genomics, University of Manchester, UK, Manchester, United Kingdom
w Department of Pathology, Massachusetts General Hospital, Boston, MA
x Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA
y Department of Neurology, Boston Children’s Hospital, Boston, MA
z Medical Genetics, University of Utah, Salt Lake City, UT
aa Institute of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria
ab Departments of Neurology and Pediatrics, NYU Langone Health, New York, NY
ac Clinical Genetics, (Formerly) Manchester Center for Genomic Medicine, Manchester University Hospitals, Manchester University NHS Foundation Trust, Manchester, United Kingdom
ad Service de Dermatologie, Assistance Publique-Hôpital Paris (AP-HP), Hôpital Henri-Mondor, UPEC, Créteil, France
Abstract
Purpose: Neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) are genetically distinct tumor predisposition syndromes with overlapping phenotypes. We sought to update the diagnostic criteria for NF2 and SWN by incorporating recent advances in genetics, ophthalmology, neuropathology, and neuroimaging. Methods: We used a multistep process, beginning with a Delphi method involving global disease experts and subsequently involving non-neurofibromatosis clinical experts, patients, and foundations/patient advocacy groups. Results: We reached consensus on the minimal clinical and genetic criteria for diagnosing NF2 and SWN. These criteria incorporate mosaic forms of these conditions. In addition, we recommend updated nomenclature for these disorders to emphasize their phenotypic overlap and to minimize misdiagnosis with neurofibromatosis type 1. Conclusion: The updated criteria for NF2 and SWN incorporate clinical features and genetic testing, with a focus on using molecular data to differentiate the 2 conditions. It is likely that continued refinement of these new criteria will be necessary as investigators study the diagnostic properties of the revised criteria and identify new genes associated with SWN. In the revised nomenclature, the term “neurofibromatosis 2” has been retired to improve diagnostic specificity. © 2022
Author Keywords
lztr1; Neurofibromatosis; NF2; Schwannomatosis; SMARCB1
Funding details
National Institutes of HealthNIH5R01CA201130-04
U.S. Department of DefenseDOD
Children’s Tumor FoundationCTF
AstraZeneca
Manchester Biomedical Research CentreBRCIS-BRC-1215-20007
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Bertelli, J.A.a , Hill, E.J.R.b , Arami, A.c , Seltser, A.c
a Governador Celso Ramos Hospital, Florianópolis, Brazil
b Washington University in St. LouisMO, United States
c Tel Aviv University, Ramat Gan, Israel
Abstract
We report a case of a bilateral glass injury to the wrist with transection of flexor tendons and the ulnar nerve and artery in a 60-year-old male patient. Two days after his accident, we repaired all divided structures, and on the right hand, we added the transfer of the opponens motor branch to the deep terminal division of the ulnar nerve aimed at first dorsal interosseous and adductor pollicis muscle reinnervation. After surgery, the patient was followed over 24 months. Postoperative dynamometry of the hand, which included grasping, key-pinch, subterminal-key-pinch, pinch-to-zoom, and first dorsal interosseous muscle strength, indicated recovery only in the nerve transfer side. © The Author(s) 2022.
Author Keywords
first dorsal interosseous muscle; nerve graft; nerve transfer; ulnar nerve paralysis
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
The Future of AD Clinical Trials with the Advent of Anti-Amyloid Therapies: An CTAD Task Force Report
(2022) Journal of Prevention of Alzheimer’s Disease, .
Delrieu, J.a b h , Bateman, R.J.c d , Touchon, J.e , Sabbagh, M.f , Cummings, J.g
a Maintain Aging Research team, CERPOP, Université de Toulouse, Inserm, Université Paul Sabatier, Toulouse, France
b Toulouse CHU, Toulouse, France
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
d Dominantly Inherited Alzheimer Network Trials Unit, Washington University School of Medicine, St. Louis, MO, United States
e University of Montpellier, Montpellier, France
f Barrow Neurological Institute, Phoenix, AZ, United States
g Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas., Las Vegas, NV 89154, United States
h Pôle gériatrie, Cité de la santé, Place Lange – TSA 60033 – 31059 Toulouse Cedex 9, INSERM UMR 1027, faculté de médecine, 37 allées Jules Guesde, Toulouse, 31000, France
Abstract
BACKGROUND: Aducanumab (ADUHELM™) was approved for the treatment of Alzheimer’s disease (AD) in the US. This approval was supported by an effect on the cerebral amyloid plaque load and evidence of cognitive efficacy to be confirmed in post-marketing trials. Other anti-amyloid antibodies are under investigation in phase III (donanemab, lecanemab, gantenerumab) and have shown preliminary evidence of a cognitive benefit in phase II trials. Although these agents target a small segment of patients with mild cognitive impairment due to AD or mild AD dementia, their advent will change the design of future clinical trials both for anti-amyloid and non-amyloid drugs. These changes will promote the selection of patients in clinical trials by amyloid and tau biomarkers that identify patients with appropriate biology and may follow the treatment response to approved amyloid antibodies. The use of these agents creates the opportunity to test combined drug therapies and to conduct comparative assessments with innovative therapies and newly approved drugs available in clinical practice. Blood-based AD biomarkers should be implemented in research and could facilitate the recruitment into clinical trials. Anti-amyloid antibodies will have positive (e.g., more early diagnosis) and negative impacts (some subjects will be reluctant to participate in trials and risk assignment to placebo) on AD trials in the immediate future. We present the results of the CTAD Task Force on this topic, in Boston, November 6, 2021. © 2022, The Author(s).
Author Keywords
Alzheimer disease; anti-amyloid therapy; biomarker; clinical trial
Funding details
National Institutes of HealthNIH
National Institute on AgingNIA
National Institute of General Medical SciencesNIGMSP20GM109025
National Institute of Neurological Disorders and StrokeNINDSP20AG068053, R01AG053798, R35AG71476, U01NS093334
Alzheimer’s AssociationAA
Bristol-Myers SquibbBMS
Alzheimer’s Drug Discovery FoundationADDF
Biogen
AbbVie
F. Hoffmann-La Roche
GHR FoundationGHR
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Topographic organization underlies intrinsic and morphological heterogeneity of central amygdala neurons expressing corticotropin-releasing hormone
(2022) Journal of Comparative Neurology, .
Li, J.-N.a b c , Chen, K.a c d , Sheets, P.L.a c
a Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, United States
b Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, United States
c Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United States
d Zionsville Community High School, Zionsville, IN, United States
Abstract
The central nucleus of the amygdala (CeA) network consists of a heterogeneous population of inhibitory GABAergic neurons distributed across distinct subregions. While the specific roles for molecularly defined CeA neurons have been extensively studied, our understanding of functional heterogeneity within classes of molecularly distinct CeA neurons remains incomplete. In addition, manipulation of genetically defined CeA neurons has produced inconsistent behavioral results potentially due to broad targeting across CeA subregions. Therefore, elucidating heterogeneity within molecularly defined neurons in subdivisions of the CeA is pivotal for gaining a complete understanding of how CeA circuits function. Here, we used a multifaceted approach involving transgenic reporter mice, brain slice electrophysiology, and neuronal morphology to dissect the heterogeneity of corticotropin-releasing hormone (CRH) neurons in topographically distinct subregions of the CeA. Our results revealed that intrinsic and morphological properties of CRH-expressing (CRH+) neurons in the lateral (CeL) and medial (CeM) subdivisions of the CeA were significantly different. We found that CeL-CRH+ neurons are relatively homogeneous in morphology and firing profile. Conversely, CeM-CRH+ neurons displayed heterogeneous electrophysiological and morphological phenotypes. Overall, these results show phenotypic differences between CRH+ neurons in CeL and CeM. © 2022 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLC.
Author Keywords
central amygdala; corticotropin-releasing hormone; intrinsic properties; morphology; topography
Funding details
National Institutes of HealthNIHR01‐R01‐NS112632
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Changes in Patient-Reported Pain Interference After Surgical Treatment of Painful Lower Extremity Neuromas
(2022) Journal of Hand Surgery Global Online, .
Liebendorfer, A., Ochoa, E., Dy, C.J.
Washington University in Saint Louis School of Medicine, MO, St Louis
Abstract
Purpose: Painful neuromas commonly cause neuropathic pain, in up to 1 in 20 cases of traumatic or iatrogenic nerve injury. Despite the multiple surgical treatment types that reduce pain, no type has been universally accepted. Methods: We performed a retrospective cohort study by administering follow-up surveys to all surgical patients treated in our department for lower-extremity neuroma from September 1, 2015, to October 22, 2021, that could be contacted, excluding those with Morton neuroma. In addition to the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI) questionnaire, survey questions covered the time to pain reduction, use of physical or occupational therapy, and characteristics of the pain. When available, previously collected preoperative and postoperative PROMIS PI data were used for patients who could not be contacted for the telephone survey. Paired-sample nonparametric testing was used to compare preoperative and postoperative PROMIS PI scores. Results: Initial query in the medical record by Current Procedural Terminology codes yielded 1,812 patients for chart review, of whom 33 were eligible to call. In total, 9 (27%) patients completed both preoperative and postoperative PROMIS PIs: 6 (18.2%) completed full telephone surveys and 3 (9.1%) had preoperative and postoperative PROMIS PI data in the chart review but could not be contacted for the full telephone survey. Four of the 6 telephone-survey respondents reported pain reduction within 12 months of their surgery. Wilcoxon signed-rank testing demonstrated a moderate but nonstatistically significant reduction in PROMIS PI scores, with a median difference of −4.85 (P = .1; 95% CI −12 to 1.2). Conclusions: There were notable improvements in our cohort, but larger studies are needed to determine whether surgical treatment of lower-extremity neuroma results in a clinically important and significant difference in PROMIS PI scores, as well as to discern the advantages each treatment. Type of study/level of evidence: Therapeutic IV. © 2022 The Authors
Author Keywords
Nerve pain; Nerve surgery; Neuralgia; Neuroma; Neuropathy
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Incidence of amyotrophic lateral sclerosis in older adults
(2022) Muscle and Nerve, .
Camacho-Soto, A.a , Searles Nielsen, S.a , Faust, I.M.a , Bucelli, R.C.a , Miller, T.M.a , Racette, B.A.a b c
a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
c Department of Neurology, Barrow Neurological Institute, Phoenix, AZ, United States
Abstract
Introduction/Aims: We investigated the age- and sex-specific incidence and survival of Medicare beneficiaries with amyotrophic lateral sclerosis (ALS) in patients 66 to 90 years of age. Methods: We identified all incident ALS cases within a population-based sample of Medicare beneficiaries in 2009 (total: 22 000 177 person-years at risk for ALS). We calculated age- and sex-specific incidence in 2009 according to multiple, progressively more stringent case definitions. Our most inclusive definition required one ALS code, whereas the most restrictive definition required at least one additional ALS code more than 6 months after the first code, including one from a neurologist. We identified associated imaging studies and electrodiagnostic testing and followed all cases through the end of 2014 to determine survival. Results: The overall incidence for our most inclusive definition was 22.84 per 100 000 person-years for men and 16.05 per 100 000 person-years for women. The overall incidence was 5.72 per 100 000 person-years for men and 3.99 per 100 000 person-years for women for our most restrictive definition. For our most inclusive definition, fewer than 39.7% of cases ever had an ALS diagnosis from a neurologist, more than 50% had an electrodiagnostic test or imaging study, and 40.1% survived less than 1 year after diagnosis, with 25.5% of these cases surviving no more than 6 months. Cases not meeting the most restrictive definition were more likely than those who did meet the restrictive definition to be older, black, or Asian. Discussion: The oldest and marginalized Medicare beneficiaries diagnosed with ALS are less likely to be included in epidemiological studies with restrictive definitions, but future studies will need to assess the accuracy of diagnosis. © 2022 Wiley Periodicals LLC.
Author Keywords
amyotrophic lateral sclerosis; epidemiology; Medicare; motor neuron disease; older adults
Funding details
National Institutes of HealthNIH
National Institute of Neurological Disorders and StrokeNINDSR01NS078398
National Institute of Environmental Health SciencesNIEHSK01ES028295
Doris Duke Charitable FoundationDDCF2015215
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
The Weekly Calendar Planning Activity to Assess Functional Cognition in Parkinson Disease
(2022) OTJR Occupation, Participation and Health, .
Foster, E.R.a , Carson, L.a , Jonas, J.a , Kang, E.a , Doty, T.a , Toglia, J.b
a Washington University in St. LouisMO, United States
b Mercy College, Dobbs Ferry, NY, United States
Abstract
The Weekly Calendar Planning Activity (WCPA) may improve understanding of functional cognition in people with Parkinson disease (PwPD) without dementia. We aimed to determine if WCPA performance (a) discriminates between PwPD with and without cognitive impairment and healthy controls and (b) correlates with other indicators of cognition and daily function. This was a cross-sectional study. Parkinson disease (PD) participants without dementia were divided into normal cognition (PD-NC, n = 25) and possible mild cognitive impairment (PD-MCI, n = 21) groups. Their WCPA performance was compared with that of a normative sample (n = 196) and correlated with neuropsychological test performance and self-reported cognition and participation. Both the PD-MCI and PD-NC groups had impaired WCPA performance. WCPA performance correlated with executive function, processing speed, and self-reported cognition and participation. The WCPA can detect functional cognitive deficits in PwPD without dementia and can inform occupational therapy interventions to support functional cognition, occupational performance, and participation in this population. © The Author(s) 2022.
Author Keywords
assessment; cognition; cognitive impairment; executive function; Parkinson’s disease
Funding details
National Institutes of HealthNIHR21AG063974
American Parkinson Disease AssociationAPDA
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access to health services among sexual minority people in the United States
(2022) Health and Social Care in the Community, .
Green, D.C.a , Parra, L.A.b , Goldbach, J.T.b
a School of Social Work, Salisbury University, Salisbury, MD, United States
b Brown School, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Sexual minority people in the United States are less likely to have access to health services when compared to their heterosexual counterparts. Less is known about the within-group sociodemographic memberships among sexual minority people regarding access to health services. Using data from a nationally representative sample, a series of univariate and bivariate analyses were used to determine associations between sociodemographic group membership and access to health services. Results suggest there are significant differences in access to health services within the sexual minority population. Differences in access to health services when considering sex-at-birth, sexual identity, age, race/ethnicity, urbanicity, education level and income status were found. These findings offer insight into the role sociodemographic group membership has on the equity of access to health services. Specifically, results indicated that disproportionate access to health services among sexual minority people were more pronounced among those with group membership who experience social marginalisation. This was particularly true for sexual minority people who were bisexual, younger, Black and Latinx, lower-income earners and sexual minority people with less education attainment. Results from this study may be used to inform policies and practices aimed at improving access to health services including, but not limited to, the expansion of the Affordable Care Act and continued development of Federally Qualified Health Centers, while acknowledging the role of within-group differences among sexual minority people. © 2022 John Wiley & Sons Ltd.
Author Keywords
access to healthcare; diversity; health care; health disparities; minority stress; primary healthcare; sexual minority people
Funding details
National Institutes of HealthNIH
Office of Behavioral and Social Sciences ResearchOBSSR
Office of Research on Women’s HealthORWH
Council on Social Work EducationCSWE
National Association of Social Workers FoundationNASWF
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD1R01HD078526
Document Type: Article
Publication Stage: Article in Press
Source: Scopus