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May 2022; 9 (3) Research ArticleOpen Access

Cryptococcal Meningitis Reported With Fingolimod Treatment

Case Series

Maurizio Del Poeta, Brian J. Ward, Benjamin Greenberg, Bernhard Hemmer, Bruce A.C. Cree, Sreelatha Komatireddy, Jitendriya Mishra, Roseanne Sullivan, Ajay Kilaru, Alan Moore, Thomas Hach, Joseph R. Berger
First published March 22, 2022, DOI: https://doi.org/10.1212/NXI.0000000000001156
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Article Information

vol. 9 no. 3 e1156
DOI: 
https://doi.org/10.1212/NXI.0000000000001156
PubMed: 
35318259
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received September 3, 2021
  • Accepted in final form January 19, 2022
  • First Published March 22, 2022.
Copyright & Usage: 
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Author Disclosures

    1. Maurizio Del Poeta, MD (maurizio.delpoeta{at}stonybrook.edu),
    2. Brian J. Ward, MDCM (brian.ward{at}mcgill.ca),
    3. Benjamin Greenberg, MD, MHS, FANA, FAAN, CRND (benjamin.greenberg{at}utsouthwestern.edu),
    4. Bernhard Hemmer, MD (hemmer{at}tum.de),
    5. Bruce A.C. Cree, MD, PhD (bruce.cree{at}ucsf.edu),
    6. Sreelatha Komatireddy, MSc, PhD (sreelatha.komatireddy{at}novartis.com),
    7. Jitendriya Mishra, MPharm, PhD (jitendriya.mishra{at}novartis.com),
    8. Roseanne Sullivan, PharmD (roseanne.sullivan{at}novartis.com),
    9. Ajay Kilaru, MD (ajay.kilaru{at}novartis.com),
    10. Alan Moore, MSc Biometry (alan.moore{at}novartis.com),
    11. Thomas Hach, MD (thomas.hach{at}novartis.com) and
    12. Joseph R. Berger, MD, FACP, FAAN, FANA
  1. Maurizio Del Poeta, MD (maurizio.delpoeta{at}stonybrook.edu),
    2. Scientific Advisory Boards:

    1. Maurizio Del Poeta is a cofounder and Chief Scientific Officer (CSO) of MicroRid Technologies, Inc.

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. JBC (editorial board member)

    Patents:

    1. 1) US No. 60/802,678 New Methods for Diagnosis and Treatment of Fungal Infections. Filed 09/01/2010 2) US No. 62/058,622 Glucosylceramide as a vaccine for fungal infection – Filed 10/01/2014 3) US No. 62/088,914 Antifungal targeting the synthesis of fungal sphingolipids. Filed 12/08/2014 4) US No. 62/192,459 New antifungals against fungal sphingolipids. Filed 07/14/2015 5) US No. 62/372,894 Vaccine compositions against pathogenic fungi. Filed 8/10/2016 6) US No. 62/473,742 Inhibiting fungal ceramide synthase as antifungal treatment. Filed 07/26/2016. 7) US No. 15/534,353. Antifungals targeting the synthesis of fungal sphingolipids. Filed 06/08/17. 8) US No. 62/521,069 Anti-Fungal Compounds Targeting the Synthesis of Fungal Sphingolipids. Filed 8/16/18. 9) US No 15/673,937 Vaccine compositions against pathogenic fungi and methods for use thereof. Filed 08/10/2017 10) US No. 16/495,605 Methods of inhibiting fungal ceramide synthase for treatment of cryptococcus neoformans infection. File 09/19/19

    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

  2. Brian J. Ward, MDCM (brian.ward{at}mcgill.ca),
    3. Scientific Advisory Boards:

    1. Serve on expert committee for Novartis to review infectious disease complications of disease-modifying therapies

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Occasional speaker fees for talks related to infectious diseases and vaccine use in people taking of disease-modifying therapies and vaccine use

    Editorial Boards:

    1. NONE

    Patents:

    1. 1) Non-binding influenza hemagglutinin proteins as improved vaccine antigens 2) Attenuated Salmonella Typhimurium-vectored vaccine for C. parvum 3) Attenuated Salmonella Typhimurium-vectored vaccine for Schistosoma mansoni prevention and treatment

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. Serve as medical officer for Medicago Inc since 2009, a biotechnology company making vaccines and monoclonal antibodies in plants (no commercial products)

    Consultancies:

    1. Serve as an ad hoc consultant for Novartis to address questions from practitioners related to infectious disease complications of disease-modifying therapies

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. 1) Medicago Inc: Academic-Industry award for studies related to plant-based virus-like particle vaccines 2) CArrier Therapeutics: Academic-Industry award for studies related to oral vaccine delivery

    Research Support, Government Entities:

    1. 1) GlycoNet: CIHR Netwok of Excellence, principal investigaor 2021-2023 2) Canadian Immunization Research Network: CIRN Network, principal investigator 2021-2023

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Hewitt Foundation: principal investigator 2021-2023

    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

  3. Benjamin Greenberg, MD, MHS, FANA, FAAN, CRND (benjamin.greenberg{at}utsouthwestern.edu),
    4. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. Dr. Greenberg has filed patents on the use of antibody biology in multiple sclerosis

    Publishing Royalties:

    1. Transverse Myelitis, UpToDate

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Novartis, Alexion, EMD Serono, Genentech, Horizon Therapeutics, Signant Health, IQVIA, PRIME ED, Immunovant, Sanofi/Genzyme, Rubin Anders

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. CLENE Nanomedicine, Anokion

    Research Support, Government Entities:

    1. NIH RO1 NS071463, Co-investigator 2012-14, PCORI, PI, 2013-2020

    Research Support, Academic Entities:

    1. Unviersity of Texas Southwestern

    Research Support, Foundations and Societies:

    1. Guthy Jackson Foundation, Siegel Rare Neuroimmune Association, National MS Society

    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. Expert witness in patent litigation involving Mylan

  4. Bernhard Hemmer, MD (hemmer{at}tum.de),
    5. Scientific Advisory Boards:

    1. Advisory Boards for Novartis, he has served as DSMB member for AllergyCare, TG Therapeutics and Polpharma Biologics

    Gifts:

    1. Me or my institution have received speaker honoraria from Desitin

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Editorial board member of Experimental Neurology and Multiple sclerosis Journal

    Patents:

    1. I hold part of two patents; one for the detection of antibodies and T cells against KIR4.1 in a subpopulati on of MS patients and one for genetic determinants of neutralizing antibodies to interferon beta

    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. Regeneron - not related

    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

  5. Bruce A.C. Cree, MD, PhD (bruce.cree{at}ucsf.edu),
    6. 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. Alexion, Atara, Autobahn, Avotres, Biogen, EMD Serono, Novartis, Sanofi, TG Therapeutics and Therini

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Genentech

    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

  6. Sreelatha Komatireddy, MSc, PhD (sreelatha.komatireddy{at}novartis.com),
    7. 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. Employee of Novartis Healthcare Private Limited, India

    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

  7. Jitendriya Mishra, MPharm, PhD (jitendriya.mishra{at}novartis.com),
    8. 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. Novartis Healthcare Pvt. Ltd., Hyderabad, India., 7 years

    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

  8. Roseanne Sullivan, PharmD (roseanne.sullivan{at}novartis.com),
    9. 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. Novartis Pharmaceutical Company Sr. Medical Safety Lead 4 years

    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

  9. Ajay Kilaru, MD (ajay.kilaru{at}novartis.com),
    10. 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

  10. Alan Moore, MSc Biometry (alan.moore{at}novartis.com),
    11. 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. Novartis Pharma AG, Basel 35 years employed

    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. I have shares in Novartis AG, Basel

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  11. Thomas Hach, MD (thomas.hach{at}novartis.com) and
    12. 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. Employed by Novartis Pharma AG, Basel.

    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. Stock of Novartis Pharma AG

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  12. Joseph R. Berger, MD, FACP, FAAN, FANA
    13. Scientific Advisory Boards:

    1. Dr. Berger has received personal compensation for serving on a Scientific Advisory or Data Safety Monitoring board for (1) MAPI and (2) ExcisionBio.

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Dr. Berger has received personal compensation an Editor, Associate Editor, or Editorial Advisory Board Member for (1) WebMD 2019-present.

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Dr. Berger has received personal compensation for serving as a Consultant for (1) Celegene/BMS; (2) Cellevolve; (3) EMD Serono/Merck; (4) Genentech; (5) Genzyme; (6) Janssen/J&J; (7) Morphic; (8) NeuVIR; (9) Novartis; (10) Roche; (11) Sanofi; (12) Takeda; (13) TG Therapeutics.

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. The institution of Dr. Berger has received research support from Biogen and from Genentech/Roche.

    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. Biogen, defense of patent, 2021

  1. From the Department of Microbiology and Immunology (M.D.P.), Stony Brook University; Division of Infectious Diseases (M.D.P.), School of Medicine, Stony Brook University; Veterans Affairs Medical Center (M.D.P.), Northport, NY; Infectious Diseases Division (B.J.W.), Research Institute of the McGill University Health Centre, Montreal, QC, Canada; University of Texas Southwestern Medical Center (B.G.), Department of Neurology, Dallas, TX; Department of Neurology (B.H.), Klinikum Rechts der Isar, Technical University of Munich; Munich Cluster for Systems Neurology (SyNergy) (B.H.), Germany; UCSF Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Novartis Healthcare Pvt. Ltd. (S.K., J.M.), Hyderabad, India; Novartis Pharmaceuticals Corporation (R.S.), East Hanover, NJ; Novartis Pharma AG (A.K., A.M., T.H.), Basel, Switzerland; and Department of Neurology (J.R.B.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
  1. Correspondence
    Dr. Berger joseph.berger{at}pennmedicine.upenn.edu
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