List of publications for July 5, 2022
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
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
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
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
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