Progressive neurodegeneration in patients with primary immunodeficiency disease on IVIG treatment

Ulrike H.M. Ziegner, Roger H. Kobayashi, Charlotte Cunningham-Rundles, Teresa Español, Anders Fasth, Anna Huttenlocher, Paul Krogstad, Lars Marthinsen, Luigi D. Notarangelo, Srdjan Pasic, Christian H.L. Rieger, Peter Rudge, Raman Sankar, Ann O. Shigeoka, E. Richard Stiehm, Kathleen E. Sullivan, A. David Webster, Hans D. Ochs

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64 Scopus citations


We have identified 14 patients with diverse primary immunodeficiencies who have developed progressive neurodegeneration of unknown etiology. All patients had received immunoglobulin replacement therapy for a mean duration of 6.5 years (range of 0.5-13.5 years) at the time of first neurological symptoms. Diagnostic tests of blood and cerebrospinal fluid analyses included chemistry, cultures, PCR for viral genomes, and cytology. In addition, neuroimaging and electrophysiologic studies were performed. Brain tissue histology (n = 5) revealed nonspecific encephalitis with microglial infiltration and neuronal loss. Twelve patients died 6 months to 15 years (median 4.3 years) after onset of neurologic findings. No evidence of any infectious disease that could have explained our patients' progressive encephalopathy was found either during their lifetimes or postmortem. These patients may have had an unusual manifestation of primary immunodeficiency diseases, an autoimmune reaction against neuronal tissue, a yet undefined infectious agent, or a complication of IVIG therapy. To help determine the etiology of this rare complication, an international surveillance system for primary immunodeficiency patients who develop progressive neurodegeneration of unknown cause is recommended.

Original languageEnglish
Pages (from-to)19-24
Number of pages6
JournalClinical Immunology
Issue number1
StatePublished - 2002


  • Idiopathic encephalopathy
  • Intravenous immunoglobulin (IVIG)
  • Primary immunodeficiency disease (PID)
  • Progressive neurodegeneration


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