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Abstract

A minority of headache patients have a secondary headache disorder. The medical literature presents and promotes red flags to increase the likelihood of identifying a secondary etiology. In this review, we aim to discuss the incidence and prevalence of secondary headaches as well as the data on sensitivity, specificity, and predictive value of red flags for secondary headaches. We review the following red flags: (1) systemic symptoms including fever; (2) neoplasm history; (3) neurologic deficit (including decreased consciousness); (4) sudden or abrupt onset; (5) older age (onset after 65 years); (6) pattern change or recent onset of new headache; (7) positional headache; (8) precipitated by sneezing, coughing, or exercise; (9) papilledema; (10) progressive headache and atypical presentations; (11) pregnancy or puerperium; (12) painful eye with autonomic features; (13) posttraumatic onset of headache; (14) pathology of the immune system such as HIV; (15) painkiller overuse or new drug at onset of headache. Using the systematic SNNOOP10 list to screen new headache patients will presumably increase the likelihood of detecting a secondary cause. The lack of prospective epidemiologic studies on red flags and the low incidence of many secondary headaches leave many questions unanswered and call for large prospective studies. A validated screening tool could reduce unneeded neuroimaging and costs.

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Publication history

Received by Neurology April 15, 2018. Accepted in final form August 27, 2018.

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Letters to the Editor
21 January 2019
Neuroimaging in headache: Fewer flags may improve care
James C. Johnston, Neurologist | GlobalNeurology

The article by Do et al.1 on secondary headaches is particularly relevant since headache misdiagnosis consistently remains among the most common diagnostic errors in neurology.2 However, the literature must be carefully scrutinized to avoid distorting the use of red flags and, thereby, perpetuating headache mismanagement. For example, Do et al. cited the Birmingham Study describing significant intracranial abnormalities in 2.1% of 530 patients as partial evidence for advancing flags.3 But the Birmingham Study—characterized by limited demographics, patient selection variability, and suboptimal imaging—excluded patients with abnormal imaging arbitrarily labeled insignificant, including, for example, small arachnoid cysts, despite there being no correlations between preoperative cyst volume and headache, or between postoperative reduction and clinical improvement.4 Moreover, Johnston et al.5 noted the study was “rendered meaningless by the lack of follow up to determine whether the [85.5% of] patients not imaged were subsequently found to have an intracranial abnormality.”

Neuroimaging protocols should be prudently refined through well-designed prospective studies focused on improving patient care, recognizing that a reduction of imaging through additional flags may not translate to decreased healthcare expenditure considering the enormous costs associated with headache misdiagnosis, including unnecessary medical expenses, loss of patient productivity, liability expenses, and related factors balanced against an MRI fee.5

References

  1. Do TP, Remmers A, Schytz HW, et al. Red and orange flags for secondary headaches in clinical practice: SNNOOP10 list. Neurology 2019;92:134–144.
  2. Physician Insurers Association of America. Risk Management Review (Neurology). Rockville, MD: PIAA; 2016.
  3. Clarke CE, Edwards J, Nicholl DJ, Sivaguru A. Imaging results in a consecutive series of 530 new patients in the Birmingham Headache Service. J Neurol 2010;257:1274–1278.
  4. Mørkve SH, Helland CA, Amus J, Lund-Johansen M, Wester KG. Surgical Decompression of Arachnoid Cysts Leads to Improved Quality of Life: A Prospective Study. Neurosurgery 2016; 78:613–625.
  5. Johnston JC, Wester K, Sartwelle TP. Neurological Fallacies Leading to Malpractice: A Case Studies Approach. Neurol Clin 2016;34:747–773.

Footnotes

For disclosures, please contact the editorial office at [email protected].

Information & Authors

Information

Published In

Neurology®
Volume 92Number 3January 15, 2019
Pages: 134-144
PubMed: 30587518

Publication History

Received: April 15, 2018
Accepted: August 27, 2018
Published online: December 26, 2018
Published in print: January 15, 2019

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Disclosure

T. Do, A. Remmers, H. Schytz, C. Schankin, and S. Nelson report no disclosures relevant to the manuscript. M. Obermann has received scientific support, travel support, and/or honoraria from Biogen Idec, Novartis, Sanofi/Genzyme, Pfizer, Teva, Lilly, Schwarz, and Heel; and received research grants from Allergan, Electrocore, Heel, and the German Ministry for Education and Research (BMBF). J. Hansen, A. Sinclair, A. Gantenbein, and G. Schoonman report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Study Funding

Thien Phu Do was funded by a grant from Candys Foundation. Christoph Schankin was funded by grants from German Migraine and Headache Society, Eye on Vision Foundation, and Baasch-Medicus-Stiftung.

Authors

Affiliations & Disclosures

From the Headache Diagnostic Laboratory (T.P.D., H.W.S.), Danish Headache Center and Department of Neurology (J.M.H.), Rigshospitalet-Glostrup, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark; Department of Neurology (A.R., G.G.S.), Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands; Department of Neurology (C.S.), Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Neurology and Anesthesiology/Critical Care Medicine (S.E.N.), Johns Hopkins University, Baltimore, MD; Center for Neurology (M.O.), Asklepios Hospitals Schildautal, Seesen; Department of Neurology (M.O.), University Hospital Essen, University of Duisburg-Essen, Germany; Neurometabolism (A.J.S.), Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, UK; and Neurorehabilitation (A.R.G.), RehaClinic Bad Zurzach and University of Zürich, Switzerland.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) Candys Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Angelique Remmers, MD
From the Headache Diagnostic Laboratory (T.P.D., H.W.S.), Danish Headache Center and Department of Neurology (J.M.H.), Rigshospitalet-Glostrup, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark; Department of Neurology (A.R., G.G.S.), Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands; Department of Neurology (C.S.), Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Neurology and Anesthesiology/Critical Care Medicine (S.E.N.), Johns Hopkins University, Baltimore, MD; Center for Neurology (M.O.), Asklepios Hospitals Schildautal, Seesen; Department of Neurology (M.O.), University Hospital Essen, University of Duisburg-Essen, Germany; Neurometabolism (A.J.S.), Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, UK; and Neurorehabilitation (A.R.G.), RehaClinic Bad Zurzach and University of Zürich, Switzerland.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Henrik Winther Schytz, MD, PhD, DMSc
From the Headache Diagnostic Laboratory (T.P.D., H.W.S.), Danish Headache Center and Department of Neurology (J.M.H.), Rigshospitalet-Glostrup, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark; Department of Neurology (A.R., G.G.S.), Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands; Department of Neurology (C.S.), Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Neurology and Anesthesiology/Critical Care Medicine (S.E.N.), Johns Hopkins University, Baltimore, MD; Center for Neurology (M.O.), Asklepios Hospitals Schildautal, Seesen; Department of Neurology (M.O.), University Hospital Essen, University of Duisburg-Essen, Germany; Neurometabolism (A.J.S.), Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, UK; and Neurorehabilitation (A.R.G.), RehaClinic Bad Zurzach and University of Zürich, Switzerland.
Disclosure
Scientific Advisory Boards:
1.
Part of the Scientific Advisory Board for BalancAir
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Speaking fee for Novartis
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Christoph Schankin, MD
From the Headache Diagnostic Laboratory (T.P.D., H.W.S.), Danish Headache Center and Department of Neurology (J.M.H.), Rigshospitalet-Glostrup, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark; Department of Neurology (A.R., G.G.S.), Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands; Department of Neurology (C.S.), Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Neurology and Anesthesiology/Critical Care Medicine (S.E.N.), Johns Hopkins University, Baltimore, MD; Center for Neurology (M.O.), Asklepios Hospitals Schildautal, Seesen; Department of Neurology (M.O.), University Hospital Essen, University of Duisburg-Essen, Germany; Neurometabolism (A.J.S.), Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, UK; and Neurorehabilitation (A.R.G.), RehaClinic Bad Zurzach and University of Zürich, Switzerland.
Disclosure
Scientific Advisory Boards:
1.
(1) commercial: Lilly (2) commercial: Almirall (3) commercial: Novartis
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
(1) commercial: Lilly (2) commercial: Almirall (3) commercial: Novartis
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) German Migraine and Headache Society (2) Baasch-Medicus-Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Sarah E. Nelson, MD
From the Headache Diagnostic Laboratory (T.P.D., H.W.S.), Danish Headache Center and Department of Neurology (J.M.H.), Rigshospitalet-Glostrup, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark; Department of Neurology (A.R., G.G.S.), Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands; Department of Neurology (C.S.), Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Neurology and Anesthesiology/Critical Care Medicine (S.E.N.), Johns Hopkins University, Baltimore, MD; Center for Neurology (M.O.), Asklepios Hospitals Schildautal, Seesen; Department of Neurology (M.O.), University Hospital Essen, University of Duisburg-Essen, Germany; Neurometabolism (A.J.S.), Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, UK; and Neurorehabilitation (A.R.G.), RehaClinic Bad Zurzach and University of Zürich, Switzerland.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) Daiichi Sankyo, funding for travel to conference
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
(1) Johns Hopkins University, 2016-present
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Mark Obermann, MD
From the Headache Diagnostic Laboratory (T.P.D., H.W.S.), Danish Headache Center and Department of Neurology (J.M.H.), Rigshospitalet-Glostrup, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark; Department of Neurology (A.R., G.G.S.), Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands; Department of Neurology (C.S.), Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Neurology and Anesthesiology/Critical Care Medicine (S.E.N.), Johns Hopkins University, Baltimore, MD; Center for Neurology (M.O.), Asklepios Hospitals Schildautal, Seesen; Department of Neurology (M.O.), University Hospital Essen, University of Duisburg-Essen, Germany; Neurometabolism (A.J.S.), Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, UK; and Neurorehabilitation (A.R.G.), RehaClinic Bad Zurzach and University of Zürich, Switzerland.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
supported by the German Federal Ministry of Education and Research BMBF 01EM 0513.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Jakob Møller Hansen, MD, PhD
From the Headache Diagnostic Laboratory (T.P.D., H.W.S.), Danish Headache Center and Department of Neurology (J.M.H.), Rigshospitalet-Glostrup, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark; Department of Neurology (A.R., G.G.S.), Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands; Department of Neurology (C.S.), Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Neurology and Anesthesiology/Critical Care Medicine (S.E.N.), Johns Hopkins University, Baltimore, MD; Center for Neurology (M.O.), Asklepios Hospitals Schildautal, Seesen; Department of Neurology (M.O.), University Hospital Essen, University of Duisburg-Essen, Germany; Neurometabolism (A.J.S.), Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, UK; and Neurorehabilitation (A.R.G.), RehaClinic Bad Zurzach and University of Zürich, Switzerland.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Alexandra J. Sinclair, MD, PhD
From the Headache Diagnostic Laboratory (T.P.D., H.W.S.), Danish Headache Center and Department of Neurology (J.M.H.), Rigshospitalet-Glostrup, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark; Department of Neurology (A.R., G.G.S.), Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands; Department of Neurology (C.S.), Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Neurology and Anesthesiology/Critical Care Medicine (S.E.N.), Johns Hopkins University, Baltimore, MD; Center for Neurology (M.O.), Asklepios Hospitals Schildautal, Seesen; Department of Neurology (M.O.), University Hospital Essen, University of Duisburg-Essen, Germany; Neurometabolism (A.J.S.), Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, UK; and Neurorehabilitation (A.R.G.), RehaClinic Bad Zurzach and University of Zürich, Switzerland.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
1) NIHR Clinician Scientist Fellowship (NIHR-CS-011-028) 2) Medical Research Council, UK (MR/K015184/1).
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Andreas R. Gantenbein, MD
From the Headache Diagnostic Laboratory (T.P.D., H.W.S.), Danish Headache Center and Department of Neurology (J.M.H.), Rigshospitalet-Glostrup, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark; Department of Neurology (A.R., G.G.S.), Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands; Department of Neurology (C.S.), Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Neurology and Anesthesiology/Critical Care Medicine (S.E.N.), Johns Hopkins University, Baltimore, MD; Center for Neurology (M.O.), Asklepios Hospitals Schildautal, Seesen; Department of Neurology (M.O.), University Hospital Essen, University of Duisburg-Essen, Germany; Neurometabolism (A.J.S.), Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, UK; and Neurorehabilitation (A.R.G.), RehaClinic Bad Zurzach and University of Zürich, Switzerland.
Disclosure
Scientific Advisory Boards:
1.
Almirall (commercial) Novartis (commercial) Curatis (commercial)
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Journal of clinical translational neurology, editorial advisory board, 2017 ongoing. Medscape Steering Committee for Migraine Collection Page, 2018 ongoing.
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Guus G. Schoonman, MD, PhD
From the Headache Diagnostic Laboratory (T.P.D., H.W.S.), Danish Headache Center and Department of Neurology (J.M.H.), Rigshospitalet-Glostrup, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark; Department of Neurology (A.R., G.G.S.), Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands; Department of Neurology (C.S.), Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Neurology and Anesthesiology/Critical Care Medicine (S.E.N.), Johns Hopkins University, Baltimore, MD; Center for Neurology (M.O.), Asklepios Hospitals Schildautal, Seesen; Department of Neurology (M.O.), University Hospital Essen, University of Duisburg-Essen, Germany; Neurometabolism (A.J.S.), Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, UK; and Neurorehabilitation (A.R.G.), RehaClinic Bad Zurzach and University of Zürich, Switzerland.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence Dr. Schoonman [email protected]
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

T.P. Do: drafting the original manuscript. A. Remmers: drafting the original manuscript. S. Henrik Winther: conceptualization and revising the manuscript for intellectual content. C. Schankin: conceptualization and revising the manuscript for intellectual content. S.E. Nelson: conceptualization and revising the manuscript for intellectual content. M. Obermann: conceptualization and revising the manuscript for intellectual content. J. Møller Hansen: conceptualization and revising the manuscript for intellectual content. A.J. Sinclair: conceptualization and revising the manuscript for intellectual content. A.R. Gantenbein: conceptualization and revising the manuscript for intellectual content. G.G. Schoonman: conceptualization and revising the manuscript for intellectual content.

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