A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection.
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.
Buchwald
Dedra
D
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Cheney
Paul R
PR
Peterson
Daniel L
DL
Henry
Berch
B
Wormsley
Susan B
SB
Geiger
Ann
A
Ablashi
Dharam V
DV
Salahuddin
S Zaki
SZ
Saxinger
CArl
C
Biddle
Royce
R
Kikinis
Ron
R
Jolesz
Ferenc A
FA
Folks
Thomas
T
Balachandran
N
N
Peter
James B
JB
Gallo
Robert C
RC
Komaroff
Anthony L
AL
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
D000914:Antibodies, Viral