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Axonal damage and outcome in subarachnoid haemorrhage
  1. A Petzold1,
  2. G Keir1,
  3. A Kay3,
  4. M Kerr4,
  5. E J Thompson1
  1. 1Department of Neuroimmunology, Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK
  2. 2The Tavistock Intensive Care Unit, The National Hospital for Neurology and Neurosurgery
  3. 3University Hospital Birmingham, Birmingham, UK
  4. 4National Institute of Nursing Research, National Institutes of Health, Bethesda, Maryland, USA
  1. Correspondence to:
 A Petzold
 Department of Neuroimmunology, Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK; a.petzold{at}ion.ucl.ac.uk

Abstract

Background: On the basis of preliminary evidence from patients with subarachnoid haemorrhage (SAH), axonal degeneration is thought to be an underestimated pathological feature.

Methods: A longitudinal study in 17 patients with aneurysmal SAH. Ventricular CSF was collected daily for up to 14 days. The neurofilament heavy chainSMI35 (NfHSMI35, a biomarker for axonal damage) was quantified using a standard ELISA (upper limit of normal 0.73 ng/ml). The primary outcome measure was the Glasgow Outcome Score (GOS) at 3 months.

Results: Of 148 samples from patients with SAH, pathologically high NfH levels in the CSF were found in 78 (52.7%) samples, compared with 20 (5%) of 416 samples from the reference population (p<0.0001). A pathological increase in NfH was observed in all patients with a bad outcome (GOS 1–3) compared with 8% of those with a good outcome (GOS 4–5, p<0.0001). This increase typically became significant 7 days after the haemorrhage (p<0.01). The result was confirmed by analysing the individual mean NfH concentrations in the CSF (3.45 v 0.37 ng/ml, p<0.01), and was reinforced by the inverse correlation of NfH in the CSF with the GOS (r = −0.65, p<0.01). Severity of injury was found to be correlated to NfHSMI35 levels in the CSF (World Federation of Neurological Surgeons, r = 0.63, p<0.01 and Glasgow Coma Score, r = −0.61, p<0.01).

Conclusion: Patients with SAH thus have secondary axonal degeneration, which may adversely affect their outcome.

  • GOS, Glasgow Outcome Score
  • NfH, neurofilament heavy chain
  • NfHSMI35, antibody SMI35 used to measure protein NfH
  • NfL, neurofilament light chain
  • SAH, subarachnoid haemorrhage

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Footnotes

  • Funding: Data collected at the University of Pittsburgh Medical Center were supported in part by a project funded by the NIH NINR R01NR0433.

  • Competing interests: None declared.

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