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Early Elevation of Serum Tumor Necrosis Factor-α Is Associated With Poor Outcome in Subarachnoid Hemorrhage
  1. Sherry H.-Y. Chou, MD, MMSc*,
  2. Steven K. Feske, MD*,
  3. Juli Atherton, PhD,
  4. Rachael G. Konigsberg, BA*,
  5. Philip L. De Jager, MD, PhD*,
  6. Rose Du, MD, PhD,
  7. Christopher S. Ogilvy, MD§,
  8. Eng H. Lo, PhD§,
  9. MingMing Ning, MD, MMSc§
  1. *From the Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA; †Department of Mathematics, Université du Québec à Montréal, Montreal, Canada; ‡Department of Neurosurgery, Brigham and Women’s Hospital; Harvard Medical School; and §Department of Neurology, Massachusetts General Hospital; Harvard Medical School, Boston, MA.
  1. Received June 04, 2012, and in revised form July 04, 2012.
  2. Accepted for publication July 05, 2012.
  3. Reprints: Eng H. Lo, PhD, and MingMing Ning, MD, MMSc, Department of Neurology, Massachusetts General Hospital/Harvard Medical School,15 Parkman St, Boston, MA 02114. Email: lo{at}, and ning{at}
  4. Supported by American Heart Association (10CRP2610341, Chou), Harvard Clinical Translational Research Center (5KL2RR025757, Chou), The American Federation for Medical Research (AFMR Scholar Award, Chou), and the United States National Institute of Health–National Institute of Neurological Disorders and Stroke (K23-NS073806, R37-NS37074, Lo; P01-NS55104, Lo; R21-NS52498, Ning; R01-NS48422, Ning).
  5. All authors have no financial relationships to report.


Objective Subarachnoid hemorrhage (SAH) is associated with inflammation that may mediate poor outcome in SAH. We hypothesize that elevated serum tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) are associated with vasospasm and poor outcome in SAH.

Methods In 52 consecutive SAH subjects, we compared TNF-α and IL-6 levels on post-SAH days 0 to 1, 2 to 3, 4 to 5, 6 to 8, and 10 to 14 with respect to vasospasm and to poor outcome at 3 and 6 months. Vasospasm was defined as more than 50% reduction in vessel caliber on angiography. Poor outcome was defined as modified Rankin score greater than 2.

Results Elevated TNF-α on post-SAH days 2 to 3 was associated with poor 3-month outcome (P = 0.0004). Global elevation of TNF-α over time (post-SAH days 0–14) was independently associated with poor 3-month outcome after adjusting for Hunt-and-Hess grade and age (P = 0.02). Neither cross-sectional nor IL-6 levels over time were associated with outcome. Neither TNF-α nor IL-6 levels were associated with vasospasm.

Conclusions Elevation in serum TNF-α on post-SAH days 2 to 3 and global elevation of TNF-α over time are associated with poor outcome but not with angiographic vasospasm in this small cohort. Future studies are needed to define the role of TNF-α in SAH-related brain injury and its potential as a SAH outcome biomarker.

Key Words
  • biomarker
  • subarachnoid hemorrhage
  • tumor necrosis factor alpha
  • inflammation

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