Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
    • UDDA Revision Series
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
    • UDDA Revision Series
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center
  • Home
  • Articles
  • Issues
  • COVID-19 Article Hub
  • Infographics & Video Summaries

User menu

  • My Alerts
  • Log in

Search

  • Advanced search
Neurology Neuroimmunology & Neuroinflammation
Home
A peer-reviewed clinical and translational neurology open access journal
  • My Alerts
  • Log in
Site Logo
  • Home
  • Articles
  • Issues
  • COVID-19 Article Hub
  • Infographics & Video Summaries

Share

December 2014; 1 (4) Clinical/Scientific NotesOpen Access

Vogt-Koyanagi-Harada syndrome: A novel case and brief review of focal neurologic presentations

Faheem Sheriff, Nandakumar S. Narayanan, Anita J. Huttner, Joachim M. Baehring
First published November 20, 2014, DOI: https://doi.org/10.1212/NXI.0000000000000049
Faheem Sheriff
From the Department of Neurology (F.S.), Oregon Health & Science University, Portland; Department of Neurology (N.S.N.), University of Iowa, Iowa City; and Department of Pathology (A.J.H.) and Departments of Neurology, Neurosurgery, and Medicine (J.M.B.), Yale School of Medicine, New Haven, CT.
MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nandakumar S. Narayanan
From the Department of Neurology (F.S.), Oregon Health & Science University, Portland; Department of Neurology (N.S.N.), University of Iowa, Iowa City; and Department of Pathology (A.J.H.) and Departments of Neurology, Neurosurgery, and Medicine (J.M.B.), Yale School of Medicine, New Haven, CT.
MD, PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anita J. Huttner
From the Department of Neurology (F.S.), Oregon Health & Science University, Portland; Department of Neurology (N.S.N.), University of Iowa, Iowa City; and Department of Pathology (A.J.H.) and Departments of Neurology, Neurosurgery, and Medicine (J.M.B.), Yale School of Medicine, New Haven, CT.
MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joachim M. Baehring
From the Department of Neurology (F.S.), Oregon Health & Science University, Portland; Department of Neurology (N.S.N.), University of Iowa, Iowa City; and Department of Pathology (A.J.H.) and Departments of Neurology, Neurosurgery, and Medicine (J.M.B.), Yale School of Medicine, New Haven, CT.
MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Full PDF
Citation
Vogt-Koyanagi-Harada syndrome: A novel case and brief review of focal neurologic presentations
Faheem Sheriff, Nandakumar S. Narayanan, Anita J. Huttner, Joachim M. Baehring
Neurol Neuroimmunol Neuroinflamm Dec 2014, 1 (4) e49; DOI: 10.1212/NXI.0000000000000049

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
1538

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

Vogt-Koyanagi-Harada syndrome (VKH) is a multisystemic granulomatous autoimmune disease affecting organs with high melanocyte concentrations including the eye, CNS, inner ear, and skin. Neurologic manifestations of VKH typically include aseptic meningitis and headache. Focal neurologic signs such as cranial nerve palsies, hemiparesis, and optic neuritis are relatively uncommon.

A 58-year-old Caucasian woman with a previous history of recurrent episodes of aseptic meningitis presented with a 2-week history of ataxia, hearing loss, numbness over the right cheek, and difficulty closing her right eye. A neurologic examination revealed decreased sensation in right cranial nerve V2 distribution, right peripheral facial palsy, and right hypoglossal nerve dysfunction. She had profound hearing impairment bilaterally. She also had dysdiadochokinesia and dysmetria on the right. An ophthalmologic examination revealed that her left eye had no light perception, and there were signs of phthisis bulbi, a dense cataract, and posterior synechiae. The right eye had 20/40 vision and was status post cataract extraction. There was no evidence of poliosis, vitiligo, or alopecia, and she denied prior ocular trauma.

She had an erythrocyte sedimentation rate of 41 mm/hour, normal angiotensin-converting enzyme, and a slightly elevated rheumatoid factor at 22 IU/mL. CSF analysis revealed 37 nucleated cells/mm3 (91% lymphocytes), glucose 92 mg/dL, and protein 257 mg/dL. CSF flow cytometry failed to reveal monoclonal lymphoproliferation. Infectious serologies were negative. Coronal and axial gadolinium-enhanced T1-weighted sequences showed diffuse pachymeningeal enhancement and thickening (figure, A and B). There was a heterogeneously enhancing soft tissue mass in the right cerebellopontine angle (CPA) arising from the dura on a broad base extending into the right internal auditory canal (figure, A and B). Biopsy of the frontal dura revealed a diffuse, thickened brown appearance (figure, C). Histopathologic analysis revealed an inflammatory infiltrate composed of numerous CD3-positive T lymphocytes and a few CD20-positive B lymphocytes. In addition, numerous CD68-positive macrophages were found to contain melanin, which was confirmed by Fontana-Masson staining (figure, D–F). Stains for fungi and acid-fast bacilli were negative and no granulomas were seen.

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure MRI and leptomeningeal biopsy findings in Vogt-Koyanagi-Harada syndrome involving the cerebellopontine angle

(A) Coronal and (B) axial gadolinium-enhanced T1-weighted sequences before initiation of corticosteroid therapy showing diffuse nodular pachymeningeal thickening and enhancement (red arrowheads). Also seen is a heterogeneously enhancing soft tissue mass in the right cerebellopontine angle (white arrows) extending into the internal auditory canal. Of note, there is mild truncation (or Gibbs) artifact in (A). (C–F) Pathology of leptomeningeal biopsy. (C) Gross view of surgical field, revealing diffuse brown discoloration of dura mater. (D) CD3-positive (40×) T lymphocytes are present. (E) Numerous CD68-positive (40×) macrophages (black arrows) containing melanin granules. (F) Fontana-Masson stain (100× oil immersion) demonstrates melanin granules within macrophages (light blue arrows).

During her hospitalization, she was started on IV dexamethasone 4 mg every 4 hours with a rapid taper. There was marked improvement in her ataxia and cranial neuropathies. Repeat T1 sequences with contrast showed almost complete resolution of the right CPA mass. Ten days after stopping the corticosteroids, she developed a bifrontal headache and tinnitus necessitating readmission and corticosteroid therapy. She was discharged on a gradual corticosteroid taper. Six-month follow-up revealed complete resolution of all neurologic deficits except bilateral hearing loss.

VKH typically presents with granulomatous panuveitis, the characteristic “sunset glow” fundus (due to loss of choroidal melanocytes), vitiligo, poliosis, and sensorineural hearing loss. This patient met criteria for a diagnosis of “incomplete VKH” given absence of integumentary findings.1 Melanin-laden macrophages on CSF cytology are highly suggestive.2 Occasionally in the chronic phase there may be an absence of granulomatous changes on biopsy, as seen in this case.

The antigenic targets for VKH are the tyrosinase family proteins and gp100, against which specific T cells are directed.3 This explains the predilection for melanocyte-rich organs. These CD4+ T cells may be triggered by an infectious agent; this process is facilitated by presence of certain HLA types, including HLA-DRB1*0405 and HLA DR 4/DR53, which may unmask cryptic self-epitopes on the surface of melanocyte-specific proteins and activate T cells that would otherwise be silent.3 Focal parenchymal lesions with associated neurologic deficits have been reported in relatively few VKH cases.4,–,6 One case presented with Wallenberg syndrome4 and another with brainstem encephalitis and multiple cranial nerve palsies.5 It is interesting that our patient had the highest disease burden in the CPA, given the higher concentration of melanocytes over the ventrolateral medulla in humans.7 In a recently published case, a predilection for pontomesencephalic and cerebellar areas was also noted.6

Given the paucity of reported VKH cases involving the posterior fossa, no inferences can be made at this point in time. The differential concentration of the tyrosinase family proteins in leptomeningeal melanocytes in various brain regions has not yet been studied and may hold the key to understanding why certain sites are more affected than others and may provide useful insight into other neurologic diseases affecting tyrosinase family proteins and melanocytes.

Given the potential for improved neurologic outcomes with timely immunosuppressive therapy, this disorder should be considered in the differential diagnosis of patients presenting with ocular disease and recurrent aseptic meningitis with or without focal neurologic deficits.

Acknowledgments

Acknowledgment: The authors sincerely thank Dennis Bourdette, MD, FANA, FAAN (Chair and Roy and Eulalia Swank Family Research Professor, Dept of Neurology, Oregon Health & Science University) and Daniel Gibbs, MD, PhD (Dept of Neurology, Oregon Health & Science University) for providing invaluable insight into the case.

Footnotes

  • Author contributions: Faheem Sheriff, Nandakumar Narayanan, and Joachim Baehring were involved in clinical data collection, discussion, and authoring the manuscript. Anita Huttner was involved in arriving at a histopathologic diagnosis and providing useful clinical insight into the case.

  • Study funding: No targeted funding reported.

  • Disclosure: F.G. Sheriff reports no disclosures. N.S. Narayanan has received research support from Brain and Behavior Research Foundation and Carver Medical Trust. A.J. Huttner and J.M Baehring report no disclosures. Go to Neurology.org/nn for full disclosures. The Article Processing Charge was paid by Oregon Health and Science University.

  • Received June 2, 2014.
  • Accepted in final form October 17, 2014.
  • © 2014 American Academy of Neurology

This is an open access article distributed under the terms of the Creative Commons Attribution-Noncommercial No Derivative 3.0 License, which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.

References

  1. 1.↵
    1. Rao NA,
    2. Sukavatcharin S,
    3. Tsai JH
    . Vogt-Koyanagi-Harada disease diagnostic criteria. Int Ophthalmol 2007;27:195–199.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Nakamura S,
    2. Nakazawa M,
    3. Yoshioka M
    . Melanin-laden macrophages in cerebrospinal fluid in Vogt-Koyanagi-Harada syndrome. Arch Ophthalmol 1996;114:1184–1188.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Damico FM,
    2. Bezerra FT,
    3. Silva GC,
    4. Gasparin F,
    5. Yamamoto JH
    . New insights into Vogt-Koyanagi-Harada disease. Arq Bras Oftalmol 2009;72:413–420.
    OpenUrlCrossRefPubMed
  4. 4.↵
    1. Nitta E,
    2. Takamori M
    . Wallenberg's syndrome in a case of Vogt-Koyanagi-Harada disease [in Japanese]. Rinsho Shinkeigaku 1989;29:505–508.
    OpenUrlPubMed
  5. 5.↵
    1. Hashimoto T,
    2. Takizawa H,
    3. Yukimura K,
    4. Ohta K
    . Vogt-Koyanagi-Harada disease associated with brainstem encephalitis. J Clin Neurosci 2009;16:593–595.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Loh Y
    . Basilar leptomeningitis in Vogt-Koyanagi-Harada disease. Neurology 2012;78:438–439.
    OpenUrl
  7. 7.↵
    1. Goldgeier MH,
    2. Klein LE,
    3. Klein-Angerer S,
    4. Moellmann G,
    5. Nordlund JJ
    . The distribution of melanocytes in the leptomeninges of the human brain. J Invest Dermatol 1984;82:235–238.
    OpenUrlCrossRefPubMed

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Disclosures
Advertisement

Association of Mediterranean-DASH Intervention for Neurodegenerative Delay and Mediterranean Diets With Alzheimer Disease Pathology

Dr. Babak Hooshmand and Dr. David Smith

► Watch

Related Articles

  • No related articles found.

Topics Discussed

  • Autoimmune diseases

Alert Me

  • Alert me when eletters are published

Recommended articles

  • Resident and Fellow Section
    Pearls & Oy-sters: A rare presentation of chronic intracranial hypertension with concurrent deafness and blindness
    Mersedeh Bahr Hosseini, Laura Stone McGuire, Milena Stosic et al.
    Neurology, July 18, 2016
  • Articles
    Hyperventilation-induced nystagmus in peripheral vestibulopathy and cerebellopontine angle tumor
    K-D Choi, J. S. Kim, H-J Kim et al.
    Neurology, September 04, 2007
  • Resident & Fellow Section
    Clinical Reasoning: Immunocompetent patient with multiple cranial nerve palsies, ataxia, and cognitive decline
    Minali Nigam, Michael Wang, Leah Commander et al.
    Neurology, January 13, 2020
  • Resident and Fellow Section
    Clinical Reasoning: A 37-year-old man with multiple cranial neuropathies
    Sean O'Loghlen, Brent Guy, John P. Rossiter et al.
    Neurology, February 15, 2016
Neurology - Neuroimmunology Neuroinflammation: 10 (6)

Articles

  • Articles
  • Issues
  • Popular Articles

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Education
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology: Neuroimmunology & Neuroinflammation
Online ISSN: 2332-7812

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise