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May 1, 2020
Letter to the Editor

COVID-19 presenting with ophthalmoparesis from cranial nerve palsy

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Marc Dinkin, MD, Virginia Gao, MD, PhD, Joshua Kahan, MBBS, PhD, Sarah Bobker, MD, Marialaura Simonetto, MD, Paul Wechsler, MD, Jasmin Harpe, MD, Christine Greer, MD, Gregory Mints, MD, Gayle Salama, MD, Apostolos John Tsiouris, MD, and Dana Leifer, MDAuthors Info & Affiliations
August 4, 2020 issue
95 (5) 221-223
https://doi.org/10.1212/WNL.0000000000009700
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Abstract

Neurologic complications of COVID-19 are not well described. We report 2 patients who were diagnosed with COVID-19 after presenting with diplopia and ophthalmoparesis.

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References

1.
Mao L, Wang M, Chen S, et al. Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China. JAMA Neurol. 2020;e201127.
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Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol 2020;92:552–555.
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Zhou L, Zhang M, Wang J, Gao J. Sars-Cov-2: underestimated damage to nervous system. Trav Med Infect Dis Epub 2020 Mar 24.
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Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19–associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features. Radiology; Epub 2020 Mar 31.
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Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 2020;367:1260–1263.
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Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? Lancet Neurol 2020;19(5):383–384.
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Letters to the Editor
9 June 2020
Author response: COVID-19 presenting with ophthalmoparesis from cranial nerve palsy
Marc Dinkin, Director of Neuro-Ophthalmology| Weill Cornell Medical College, New York Presbyterian Hospital
Virginia Gao, Neurology resident| Weill Cornell Medical College, New York Presbyterian Hospital
Sarah Bobker, Neurology resident| Weill Cornell Medical College, New York Presbyterian Hospital
Marialaura Simonetto, Resident Physician| Weill Cornell Medical College, New York Presbyterian Hospital
Paul Wechsler, Neurology resident| Weill Cornell Medical College, New York Presbyterian Hospital
Jasmin Harpe, Neurology resident| Weill Cornell Medical College, New York Presbyterian Hospital
Christine Greer, Neuro-ophthalmology fellow| Weill Cornell Medical College, New York Presbyterian Hospital
Gregory Mints, Internal Medicine Physician| Weill Cornell Medical College, New York Presbyterian Hospital
Gayle Salama, Radiologist| Weill Cornell Medical College, New York Presbyterian Hospital
Apostolos J Tsiouris, Neuroradiologist| Weill Cornell Medical College, New York Presbyterian Hospital
Dana Leifer, Neurologist| Weill Cornell Medical College, New York Presbyterian Hospital
Joshua Kahan, MD| Weill Cornell Neurology (New York)

We appreciate Dr. Machado’s insightful comments regarding our case series1 describing cranial neuropathies in two patients with COVID-19. The triad of progressive ophthalmoplegia, ataxia, and areflexia in our first case suggested Miller Fisher syndrome (MFS), despite the negative ganglioside panel, although we were surprised by the short interval of 4 days between respiratory and neurologic symptoms. However, in two cases of COVID-19 associated MFS, latencies were similar (5 and 3 days),2 suggesting that the post-infectious interval is shorter for COVID-19 than for other infections. In fact, in a recent case of Guillain-Barré syndrome associated with COVID-19, neurologic symptoms preceded the respiratory symptoms by one week.3 The authors noted that lymphopenia was present upon admission, indicating presence of COVID-19 long before systemic symptoms began. This is in line with recent observations that 10/13 nursing home residents only developed symptoms seven days after testing positive.4 Our second case may reflect direct viral invasion as there were no signs of MFS. Transfer of the virus through the olfactory bulbs is supported by recent evidence of olfactory bulb edema5 and hyperintensity of the adjacent gyrus rectus6 in patients with COVID-19 associated anosmia, although our patient never developed anosmia. The rapid recovery of anosmia observed in most COVID-19 cases argues for olfactory epithelial dysfunction as opposed to olfactory nerve damage, and we agree with Dr. Machado that hematogenous spread of virus may also play a role in CNS disease.

Disclosure

The authors report no relevant disclosures. Contact [email protected] for full disclosures.

References

  1. Dinkin M, Gao V, Kahan J, et al. COVID-19 presenting with ophthalmoparesis from cranial nerve palsy. Neurology 2020 Epub May 1.
  2. Gutiérrez-Ortiz C, Méndez A, Rodrigo-Rey S, et al. Miller Fisher Syndrome and polyneuritis cranialis in COVID-19. Neurology 2020 Epub Apr 17.
  3. Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? Lancet Neurol 2020 May;19:383–384.
  4. Kimball A, Hatfield KM, Arons M, et al. Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility - King County, Washington, March 2020. MMWR Morb Mortal Wkly Rep 2020;69:377–81.
  5. Politi LS, Salsano E, Grimaldi M. Magnetic Resonance Imaging Alteration of the Brain in a Patient With Coronavirus Disease 2019 (COVID-19) and Anosmia. JAMA Neurol 2020 Epub May 29.
  6. Laurendon T, Radulesco T, Mugnier J, et al. Bilateral transient olfactory bulbs edema during COVID-19-related anosmia. Neurology 2020 Epub May 22.
2 June 2020
Reader response: COVID-19 presenting with ophthalmoparesis from cranial nerve palsy
Calixto Machado, Neurologist, AAN Corresponding Fellow| Insttitute of Neurology and Neurosurgery (Havana, Cuba)

Dinkin et al.1 reported two COVID-19 patients: the first case complained of subjective fever, cough and myalgias, and 4 days later showed ophthalmoparesis, leg paresthesia, and tendon areflexia; the second case suffered from cough and fever for several days and finally presented painless diplopia and abduction palsy of her right eye.

The authors argued that a virus-mediated immune response was a possible mechanism to explain patients’ symptoms1 as reported in cases of Guillain-Barré syndrome (GBS) associated with SARS-CoV-2 infection.2 The authors also considered the possibility of a direct virus infection mechanism.1

Timing in the appearance of symptoms is crucial to discuss the possible virus infection mechanism.2,3 Symptoms in GBS generally developed from 1 to 6 weeks following an upper respiratory infection or diarrheal type illness, or after vaccination.2

SARS-CoV-2 can reach CNS through hematogenous or neural propagation. Neural dissemination can be retrograde or antegrade and is facilitated by proteins called dinein and kinesin, which can be targets of viruses. Hence, SARS-CoV-2 can even invade the CNS coming from peripheral nerves.3–5

Therefore, the occurrence of neurologic symptoms within a few days of disease onset led to consideration of a possible direct virus infection mechanism, although a virus-mediated immune response can’t be excluded.

Disclosure

The author reports no relevant disclosures. Contact [email protected] for full disclosures.

References

  1. Dinkin M, Gao V, Kahan J, et al. COVID-19 presenting with ophthalmoparesis from cranial nerve palsy. Neurology 2020;DOI: 10.1212/WNL.0000000000009700.
  2. Scheidl E, Canseco DD, Hadji-Naumov A, Bereznai B. Guillain-Barre syndrome during SARS-CoV-2 pandemic: A case report and review of recent literature. J Peripher Nerv Syst 2020 Epub May 10.
  3. Machado C. Severe Covid-19 cases: Is respiratory distress partially explained by central nervous system involvement? MEDICC Rev 2020;22:38–39.
  4. Conde Cardona G, Quintana Pájaro LD, Quintero Marzola ID, Ramos Villegas Y, Moscote Salazar LR. Neurotropism of SARS-CoV 2: Mechanisms and manifestations. J Neurol Sci 2020 Epub May 15.
  5. Carod-Artal FJ. Neurological complications of coronavirus and COVID-19. Rev Neurol 2020;70:311–322.

Information & Authors

Information

Published In

Neurology®
Volume 95 • Number 5 • August 4, 2020
Pages: 221-223
PubMed: 32358218

Copyright

© 2020 American Academy of Neurology.

Publication History

Received: April 4, 2020
Accepted: April 23, 2020
Published online: May 1, 2020
Published in print: August 4, 2020

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Disclosure

The authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.

Study Funding

No targeted funding reported.

Authors

Affiliations & Disclosures

Marc Dinkin, MD
From the Department of Neurology (M.D., V.G., J.K., S.B., M.S., P.W., J.H., D.L.), Department of Ophthalmology (M.D., C.G.), Department of Medicine (G.M.) and Department of Radiology (G.S., A.J.T.), Weill Cornell Medical College, New York.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
American Austrian Foundation - speaker; travel reimbursement
Editorial Boards:
1.
Associate Editor, Journal of Neuro-Ophthalmology: no compensation Editor, Practical Neurology: no compensation Guest Editor, Continuum
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.
1) Commercial entity: Spouse works as an oncologist for a private practice medical group, CareMount Medical group.
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.
Commercial Entity,Bayer Pharmaceuticals Expert Witness for the Defense,
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Virginia Gao, MD, PhD
From the Department of Neurology (M.D., V.G., J.K., S.B., M.S., P.W., J.H., D.L.), Department of Ophthalmology (M.D., C.G.), Department of Medicine (G.M.) and Department of Radiology (G.S., A.J.T.), Weill Cornell Medical College, New York.
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
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1.
NONE
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1.
NONE
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1.
NONE
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Joshua Kahan, MBBS, PhD
From the Department of Neurology (M.D., V.G., J.K., S.B., M.S., P.W., J.H., D.L.), Department of Ophthalmology (M.D., C.G.), Department of Medicine (G.M.) and Department of Radiology (G.S., A.J.T.), Weill Cornell Medical College, New York.
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
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1.
NONE
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1.
NONE
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1.
NONE
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NONE
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Sarah Bobker, MD
From the Department of Neurology (M.D., V.G., J.K., S.B., M.S., P.W., J.H., D.L.), Department of Ophthalmology (M.D., C.G.), Department of Medicine (G.M.) and Department of Radiology (G.S., A.J.T.), Weill Cornell Medical College, New York.
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
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1.
NONE
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1.
NONE
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NONE
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Marialaura Simonetto, MD
From the Department of Neurology (M.D., V.G., J.K., S.B., M.S., P.W., J.H., D.L.), Department of Ophthalmology (M.D., C.G.), Department of Medicine (G.M.) and Department of Radiology (G.S., A.J.T.), Weill Cornell Medical College, New York.
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
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1.
NONE
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1.
NONE
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NONE
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Paul Wechsler, MD
From the Department of Neurology (M.D., V.G., J.K., S.B., M.S., P.W., J.H., D.L.), Department of Ophthalmology (M.D., C.G.), Department of Medicine (G.M.) and Department of Radiology (G.S., A.J.T.), Weill Cornell Medical College, New York.
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
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1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
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1.
NONE
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1.
NONE
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NONE
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Jasmin Harpe, MD
From the Department of Neurology (M.D., V.G., J.K., S.B., M.S., P.W., J.H., D.L.), Department of Ophthalmology (M.D., C.G.), Department of Medicine (G.M.) and Department of Radiology (G.S., A.J.T.), Weill Cornell Medical College, New York.
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
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1.
NONE
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1.
NONE
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NONE
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Christine Greer, MD
From the Department of Neurology (M.D., V.G., J.K., S.B., M.S., P.W., J.H., D.L.), Department of Ophthalmology (M.D., C.G.), Department of Medicine (G.M.) and Department of Radiology (G.S., A.J.T.), Weill Cornell Medical College, New York.
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
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1.
NONE
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1.
NONE
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Gregory Mints, MD
From the Department of Neurology (M.D., V.G., J.K., S.B., M.S., P.W., J.H., D.L.), Department of Ophthalmology (M.D., C.G.), Department of Medicine (G.M.) and Department of Radiology (G.S., A.J.T.), Weill Cornell Medical College, New York.
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
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1.
NONE
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1.
NONE
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1.
NONE
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Gayle Salama, MD
From the Department of Neurology (M.D., V.G., J.K., S.B., M.S., P.W., J.H., D.L.), Department of Ophthalmology (M.D., C.G.), Department of Medicine (G.M.) and Department of Radiology (G.S., A.J.T.), Weill Cornell Medical College, New York.
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
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NONE
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NONE
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Apostolos John Tsiouris, MD
From the Department of Neurology (M.D., V.G., J.K., S.B., M.S., P.W., J.H., D.L.), Department of Ophthalmology (M.D., C.G.), Department of Medicine (G.M.) and Department of Radiology (G.S., A.J.T.), Weill Cornell Medical College, New York.
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:
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NONE
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NONE
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Dana Leifer, MD
From the Department of Neurology (M.D., V.G., J.K., S.B., M.S., P.W., J.H., D.L.), Department of Ophthalmology (M.D., C.G.), Department of Medicine (G.M.) and Department of Radiology (G.S., A.J.T.), Weill Cornell Medical College, New York.
Disclosure
Scientific Advisory Boards:
1.
Cerevast Therapeutics (DSMB)
Gifts:
1.
NONE
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1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
(1) Gerson Lehrman Group, Inc.
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
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1.
NONE
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NONE
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NIH #NS086728, co-principal investigator, 2013- NIH #NS080824, site principal investigator, 2013- NIH #NS080168, site principal investigator, 2015- NIH #NS097876, site principal investigator, 2018- NIH #NS074425, site principal investigator, 2015- NIH #NS092076, site principal investigator, 2016-
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NONE
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NONE
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NONE
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1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
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NONE
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NONE
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Notes

Correspondence Dr. Dinkin [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.

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    • Mutasim Albattah,
    • Mohammad A Alshrouf,
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