CNS vasculitis in a patient with MS on daclizumab monotherapy

Neurology. 2013 Jan 29;80(5):453-7. doi: 10.1212/WNL.0b013e31827f0f42. Epub 2013 Jan 9.


Objective: To report the development of CNS vasculitis in a patient with multiple sclerosis (MS) treated with daclizumab.

Methods: This report includes clinical, MRI, immunologic, and pathology data and CSF analysis.

Results: After completing a phase II daclizumab monotherapy study with an optimal response as evidenced by significant decrease in MRI disease activity and stable clinical examinations, the patient elected to continue daclizumab therapy outside of NIH study. Daclizumab was discontinued after 21 doses due to the onset of new clinical symptoms and evidence of a vascular pattern of contrast enhancement on brain and spine MRI. Because of continued clinical deterioration, stereotactic brain biopsy was performed, showing small-vessel CNS vasculitis. Treatment was initiated with IV methylprednisolone followed by a regimen of cyclophosphamide. Immunologic studies suggest that unexpected lack of expansion of CD56(bright) NK cells and predictable decline in FoxP3+ T-regs combined with a transient interruption in daclizumab dosing may have contributed to this serious side effect.

Conclusions: Only safety data from larger phase III studies and potentially postmarketing experience will define the exact risk of daclizumab-induced immunopathologies. Nevertheless, our case provides plausible hypothesis and potential biomarker that may be used to screen susceptible patients and implement preventive safety measures during potentially vulnerable periods.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • CD56 Antigen / metabolism
  • Cyclophosphamide / therapeutic use
  • Daclizumab
  • Disability Evaluation
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Immunosuppressive Agents / therapeutic use*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Methylprednisolone / therapeutic use
  • Multiple Sclerosis / cerebrospinal fluid
  • Multiple Sclerosis / complications*
  • Multiple Sclerosis / diagnosis
  • Vasculitis, Central Nervous System / drug therapy*
  • Vasculitis, Central Nervous System / etiology*
  • Vasculitis, Central Nervous System / pathology


  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal, Humanized
  • CD56 Antigen
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Cyclophosphamide
  • Daclizumab
  • Methylprednisolone