72
High Cerebrospinal Fluid Neurofilament Protein Levels in AIDS Dementia Complex
Magnus Gisslén*1, P Cinque2, L Hagberg1, R Price3, L Rosengren1, and B Brew4
1Sahlgrenska Akademy, Göteborg Univ, Sweden; 2Hosp San Raffaele, San Raffaele Sci Inst, Milan, Italy; 3Univ of California, San Francisco, US; and 4St Vincent's Hosp, Sydney, Australia
Background: Cerebrospinal fluid (CSF) concentrations of the light subunit of the neurofilament protein (NFL), a major structural component
of myelinated axons, can serve as a sensitive
indicator of axonal injury in the central nervous system.
Methods: CSF NFL concentrations were measured by ELISA (normal <250 ng/L) in frozen samples from 213 HIV-infected patients without
ART; 56 with AIDS dementia complex (ADC), 46 with central nervous system
opportunistic infections or tumors (CNS OI), 95
without neurological symptoms, and 16 with primary HIV infection. The effect of
ART was studied with repeated CSF sampling on 4 of the patients with ADC.
Results: CSF NFL was significantly higher in patients with ADC (median 1885 ng/L, interquartile range 563 to 7278)
and central nervous system opportunistic infections (2315 ng/L,
993 to 6855 ng/L) than in neuroasymptomatic
patients (<250 ng/L, <250 to 326) or primary
HIV infection (<250 ng/L, <250 to 295), p <0.0001. Among patients with ADC,
those with more severe disease, stage 2 to 4, had higher levels than those with
stage 0.5 to 1, p <0.05. CSF NFL declined
to the limit of detection in the 4 ADC patients with treatment initiation in
parallel with their neurological improvement.
CSF NFL concentrations were also higher in neuroasymptomatic
patients with lower CD4-cell strata than higher, p <0.0001. Increased CSF NFL, in most cases only slightly, were
found in 27 of 59 neuroasymptomatic patients with CD4
counts <200/mL compared with 2 of 36 with
CD4-cells ≥200/mL.
Conclusions: The findings of this study support the value of CSF NFL as a useful marker
of CNS damage in HIV infection. In patients without central nervous system
opportunistic infections or tumors, elevated CSF NFL
concentrations are associated with ADC, follow the grade of severity, and
decrease after initiation of effective ART. Virtually all previously suggested CSF
markers of ADC relate to immune activation or HIV viral load. NFL is the first
marker that directly reflects brain injury; as such, CSF NFL levels should
prove to be useful in clinical practice as an objective marker of ADC.
|
