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CSF neurofilament protein (NFL) — a marker of active HIV-related neurodegeneration

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Abstract

Background and methods

The light subunit of the neurofilament protein (NFL), a major structural component of myelinated axons, is a sensitive indicator of axonal injury in the central nervous system (CNS) in a variety of neurodegenerative disorders. Cerebrospinal fluid (CSF) NFL concentrations were measured by ELISA (normal < 250 ng/l) in archived samples from 210 HIV-infected patients not taking antiretroviral treatment: 55 with AIDS dementia complex (ADC), 44 with various CNS opportunistic infections/tumours (CNS OIs), 95 without neurological symptoms or signs, and 16 with primary HIV infection (PHI). The effect of highly active antiretroviral treatment (HAART) was studied by repeated CSF sampling in four of the ADC patients initiating treatment.

Results

CSF NFL concentrations were significantly higher in patients with ADC (median 2590 ng/l, IQR 780–7360) and CNS OIs (2315 ng/l, 985–7390 ng/l) than in neuroasymptomatic patients (<250 ng/l, <250–300) or PHI (<250 ng/l, <250–280), p < 0.001. Among patients with ADC, those with more severe disease (stage 2–4) had higher levels than those with milder disease (stage 0.5–1), p < 0.01. CSF NFL declined during HAART to the limit of detection in parallel with virological response and neurological improvement in ADC.CSF NFL concentrations were higher in neuroasymptomatic patients with lower CD4-cell strata than higher, p < 0.001. This increase was less marked than in the ADC patients and noted in 26/58 neuroasymptomatic patients with CD4 counts <200/μl compared to 1/37 with CD4-cells ≥200/μl.

Conclusions

The findings of this study support the value of CSF NFL as a useful marker of ongoing CNS damage in HIV infection. Markedly elevated CSF NFL concentrations in patients without CNS OIs are associated with ADC, follow the grade of severity, and decrease after initiation of effective antiretroviral treatment. Nearly all previously suggested CSF markers of ADC relate to immune activation or HIV viral load that do not directly indicate brain injury. By contrast NFL is a sensitive marker of such injury, and should prove useful in evaluating the presence and activity of ongoing CNS injury in HIV infection.

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Authors and Affiliations

  1. Dept. of Infectious Diseases, The Sahlgrenska Academy at Göteborg University, Gothenburg, Sweden

    Sahra Abdulle MD, PhD, Åsa Mellgren MD, PhD, Lars Hagberg MD, PhD & Magnus Gisslén MD, PhD

  2. Dept. of Neurology, The Sahlgrenska Academy at Göteborg University, Gothenburg, Sweden

    Lars Rosengren MD, PhD

  3. Dept. of Neurology, St. Vincent's Hospital, University of New South Wales, Sydney, Australia

    Bruce J. Brew MBBS, MD

  4. Clinic of Infectious Diseases, San Raffaele Hospital, Milan, Italy

    Paola Cinque MD, PhD

  5. Dept. of Neurology, University of California San Francisco, San Francisco General Hospital, San Francisco, CA, USA

    Richard W. Price MD

  6. Dept. of Infectious Diseases, Sahlgrenska University Hospital/Östra, 416 85, Gothenburg, Sweden

    Magnus Gisslén MD, PhD

Authors
  1. Sahra Abdulle MD, PhD
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  2. Åsa Mellgren MD, PhD
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  3. Bruce J. Brew MBBS, MD
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  4. Paola Cinque MD, PhD
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  5. Lars Hagberg MD, PhD
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  6. Richard W. Price MD
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  7. Lars Rosengren MD, PhD
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  8. Magnus Gisslén MD, PhD
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Corresponding author

Correspondence to Magnus Gisslén MD, PhD.

Additional information

Drs. Abdulle and Mellgren contributed equally to this work.

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Abdulle, S., Mellgren, Å., Brew, B.J. et al. CSF neurofilament protein (NFL) — a marker of active HIV-related neurodegeneration. J Neurol 254, 1026–1032 (2007). https://doi.org/10.1007/s00415-006-0481-8

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  • DOI: https://doi.org/10.1007/s00415-006-0481-8

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