Prospective natural history study of

Age of Onset Amyotrophic Lateral Sclerosis / epidemiology Biomarkers / blood C9orf72 Protein / genetics DNA Repeat Expansion Female Follow-Up Studies Heterozygote Humans Longitudinal Studies Male Middle Aged Prospective Studies Retrospective Studies

Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
22 10 2019
Historique:
received: 18 12 2018
accepted: 20 05 2019
pubmed: 4 10 2019
medline: 7 2 2020
entrez: 4 10 2019
Statut: ppublish

Résumé

To define the natural history of the We prospectively collected clinical and demographic data from 116 symptomatic C9ALS and 12 non-amyotrophic lateral sclerosis (ALS) full expansion carriers across 7 institutions in the United States and the Netherlands. In addition, we collected blood samples for DNA repeat size assessment, CSF samples for biomarker identification, and autopsy samples for dipeptide repeat protein (DPR) size determination. Finally, we collected retrospective clinical data via chart review from 208 individuals with C9ALS and 450 individuals with singleton ALS. The mean age at onset in the symptomatic prospective cohort was 57.9 ± 8.3 years, and median duration of survival after onset was 36.9 months. The monthly change was -1.8 ± 1.7 for ALS Functional Rating Scale-Revised and -1.4% ± 3.24% of predicted for slow vital capacity. In blood DNA, we found that G We present a thorough investigation of C9ALS natural history, providing the basis for C9ALS clinical trial design. We found that clinical features of this genetic subset are less variant than in singleton ALS. In addition, we identified important correlations of C9ALS patient pathologies with clinical and demographic data.

Identifiants

DOI: 10.1212/WNL.0000000000008359 PMID: 31578300 PMC: PMC6946465
pubmed: 31578300
pii: WNL.0000000000008359
doi: 10.1212/WNL.0000000000008359
pmc: PMC6946465
doi:

Substances chimiques

Biomarkers 0
C9orf72 Protein 0
C9orf72 protein, human 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1605-e1617

Subventions

Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024992
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS073873
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS078398
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS088689
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002345
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS104022
Pays : United States

Informations de copyright

© 2019 American Academy of Neurology.

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Auteurs

Alexander J Cammack (AJ)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.
ORCID: 0000-0002-9624-9067

Nazem Atassi (N)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Theodore Hyman (T)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Leonard H van den Berg (LH)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Matthew Harms (M)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Robert H Baloh (RH)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Robert H Brown (RH)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Michael A van Es (MA)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Jan H Veldink (JH)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Balint S de Vries (BS)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Jeffrey D Rothstein (JD)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Caroline Drain (C)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Jennifer Jockel-Balsarotti (J)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Amber Malcolm (A)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Sonia Boodram (S)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Amber Salter (A)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Nicholas Wightman (N)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Hong Yu (H)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Alexander V Sherman (AV)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Thomas J Esparza (TJ)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Diane McKenna-Yasek (D)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Margaret A Owegi (MA)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Catherine Douthwright (C)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Alexander McCampbell (A)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Toby Ferguson (T)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Carlos Cruchaga (C)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Merit Cudkowicz (M)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA.

Timothy M Miller (TM)

From the Department of Neurology (A.J.C., T.H., C.D., J.J.-B., A.M., S.B., A.S., T.J.E., C.C., T.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (N.A., H.Y., A.V.S., M.C.), Neurological Clinical Research Institute, Massachusetts General Hospital, Boston; Department of Neurology (L.H.v.d.B., M.A.v.E., J.H.V., B.S.d.V.), Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, the Netherlands; Department of Neurology (M.H.), Columbia University, New York, NY; Department of Neurology (R.H. Baloh), Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology (R.H. Brown, N.W., D.M.-Y., M.A.O., C.D.), University of Massachusetts, Worcester; Department of Neurology (J.D.R.), Johns Hopkins University, Baltimore, MD; and Biogen Inc. (A.M., T.F.), Boston, MA. miller.t@wustl.edu.

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