title: CD40 ligand deficiency: neurologic sequelae with radiographic correlation.
abstract: Patients with CD40 ligand deficiency are susceptible to central nervous system infections, but to date the neurologic progression or long-term outcome of central nervous system complications have not been reported in detail. Characterizing the central nervous system complications of immune deficiencies can lead to the identification of new pathogens. For this study, clinical data were reviewed on patients with both CD40 ligand deficiency and neurodegeneration, identified from a larger cohort of 31 patients. Five patients had progressive neurologic and cognitive decline in the absence of clinical signs of acute fulminant encephalitis, with anatomic brain abnormalities and high mortality (60%). Despite multiple evaluations, no pathogens were identified in four patients, all of whom were on standard intravenous immunoglobulin therapy at illness presentation. This clinical phenotype of progressive decline without acute fulminant encephalitis is similar to chronic enteroviral encephalitis in X-linked agammaglobulinemia, another condition with severe humoral immune defects. Whether infection secondary to subtherapeutic levels of central nervous system immunoglobulin G (IgG), inadequately protective levels of serum IgG, or impaired CD40 ligand-dependent IgG-independent antiviral responses contributed remains undetermined. Emerging gene-chip techniques applied in patients with primary immune deficiencies may identify heretofore unknown viruses. Prospective neurocognitive and evaluation of patients with CD40 ligand deficiency may identify affected patients before overt clinical signs appear.
authors.affiliation: Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 2D54, Bethesda, MD 20892-1298, USA. shrinivas@uky.edu
authors.forename: Shrinivas
authors.initials: S
authors.lastname: Bishu
authors.forename: Deepak
authors.initials: D
authors.lastname: Madhavan
authors.forename: Phillip
authors.initials: P
authors.lastname: Perez
authors.forename: Lucy
authors.initials: L
authors.lastname: Civitello
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
authors.forename: Margaret
authors.initials: M
authors.lastname: Fessler
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.forename: Ashish
authors.initials: A
authors.lastname: Jain
authors.forename: Maryland
authors.initials: M
authors.lastname: Pao
mesh_terms: D001921:Brain / Q000473:pathology; D023201:CD40 Ligand / Q000172:deficiency*; D002675:Child, Preschool; D003072:Cognition Disorders / Q000209:etiology / Q000628:therapy; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D053307:Hyper-IgM Immunodeficiency Syndrome, Type 1 / Q000150:complications* / Q000473:pathology* / Q000628:therapy; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000473:pathology* / Q000628:therapy
chemical_list: D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D023201:CD40 Ligand