title: A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection.
abstract: To conduct neurologic, immunologic, and virologic studies in patients with a chronic debilitating illness of acute onset.
  
  
  
  Cohort study with comparison to matched, healthy control subjects.
  
  
  
  We studied 259 patients who sought care in one medical practice; 29% of the patients were regularly bedridden or shut-in.
  
  
  
  Detailed medical history, physical examination, conventional hematologic and chemistry testing, magnetic resonance imaging (MRI) studies, lymphocyte phenotyping studies, and assays for active infection of patients' lymphocytes with human herpesvirus type 6 (HHV-6).
  
  
  
  Patients had a higher mean (+/- SD) CD4/CD8 T-cell ratio than matched healthy controls (3.16 +/- 1.5 compared with 2.3 +/- 1.0, respectively; P less than 0.003). Magnetic resonance scans of the brain showed punctate, subcortical areas of high signal intensity consistent with edema or demyelination in 78% of patients (95% CI, 72% to 86%) and in 21% of controls (CI, 11% to 36%) (P less than 10(-9)). Primary cell culture of lymphocytes showed active replication of HHV-6 in 79 of 113 patients (70%; CI, 61% to 78%) and in 8 of 40 controls (20%; CI, 9% to 36%) (P less than 10(-8], a finding confirmed by assays using monoclonal antibodies specific for HHV-6 proteins and by polymerase chain reaction assays specific for HHV-6 DNA.
  
  
  
  Neurologic symptoms, MRI findings, and lymphocyte phenotyping studies suggest that the patients may have been experiencing a chronic, immunologically mediated inflammatory process of the central nervous system. The active replication of HHV-6 most likely represents reactivation of latent infection, perhaps due to immunologic dysfunction. Our study did not directly address whether HHV-6, a lymphotropic and gliotropic virus, plays a role in producing the symptoms or the immunologic and neurologic dysfunction seen in this illness. Whether the findings in our patients, who came from a relatively small geographic area, will be generalizable to other patients with a similar syndrome remains to be seen.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
authors.forename: Dedra
authors.initials: D
authors.lastname: Buchwald
authors.forename: Paul R
authors.initials: PR
authors.lastname: Cheney
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Peterson
authors.forename: Berch
authors.initials: B
authors.lastname: Henry
authors.forename: Susan B
authors.initials: SB
authors.lastname: Wormsley
authors.forename: Ann
authors.initials: A
authors.lastname: Geiger
authors.forename: Dharam V
authors.initials: DV
authors.lastname: Ablashi
authors.forename: S Zaki
authors.initials: SZ
authors.lastname: Salahuddin
authors.forename: CArl
authors.initials: C
authors.lastname: Saxinger
authors.forename: Royce
authors.initials: R
authors.lastname: Biddle
authors.forename: Ron
authors.initials: R
authors.lastname: Kikinis
authors.forename: Ferenc A
authors.initials: FA
authors.lastname: Jolesz
authors.forename: Thomas
authors.initials: T
authors.lastname: Folks
authors.forename: N
authors.initials: N
authors.lastname: Balachandran
authors.forename: James B
authors.initials: JB
authors.lastname: Peter
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gallo
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Komaroff
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D001921:Brain / Q000473:pathology; D016516:CD4-CD8 Ratio; D016000:Cluster Analysis; D015673:Fatigue Syndrome, Chronic / Q000382:microbiology*; D005260:Female; D006566:Herpesviridae Infections / Q000134:cerebrospinal fluid / Q000150:complications* / Q000276:immunology / Q000503:physiopathology; D015654:Herpesvirus 6, Human / Q000276:immunology / Q000502:physiology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral