title: Progressive neurodegeneration in patients with primary immunodeficiency disease on IVIG treatment.
abstract: 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.
authors.affiliation: Department of Pediatrics, UCLA School of Medicine, Los Angeles, California, USA. hokanson2@home.com
authors.forename: Ulrike H M
authors.initials: UH
authors.lastname: Ziegner
authors.forename: Roger H
authors.initials: RH
authors.lastname: Kobayashi
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cunningham-Rundles
authors.forename: Teresa
authors.initials: T
authors.lastname: Español
authors.forename: Anders
authors.initials: A
authors.lastname: Fasth
authors.forename: Anna
authors.initials: A
authors.lastname: Huttenlocher
authors.forename: Paul
authors.initials: P
authors.lastname: Krogstad
authors.forename: Lars
authors.initials: L
authors.lastname: Marthinsen
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Srdjan
authors.initials: S
authors.lastname: Pasic
authors.forename: Christian H L
authors.initials: CH
authors.lastname: Rieger
authors.forename: Peter
authors.initials: P
authors.lastname: Rudge
authors.forename: Raman
authors.initials: R
authors.lastname: Sankar
authors.forename: Ann O
authors.initials: AO
authors.lastname: Shigeoka
authors.forename: E Richard
authors.initials: ER
authors.lastname: Stiehm
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Sullivan
authors.forename: A David
authors.initials: AD
authors.lastname: Webster
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
mesh_terms: D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000150:complications / Q000235:genetics / Q000628:therapy; D000368:Aged; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000150:complications / Q000628:therapy; D003141:Communicable Diseases / Q000175:diagnosis; D005060:Europe; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications* / Q000628:therapy*; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000175:diagnosis*; D012189:Retrospective Studies; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000628:therapy; D014481:United States; D044465:White People