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Comment & Response
March 2017

Neurofilament Protein and Antineurofilament Antibodies Following Traumatic Brain Injury

Author Affiliations
  • 1Department of Neurology, University of Wisconsin, Madison
  • 2Kinseiology and Health Education, The University of Texas at Austin, Austin
JAMA Neurol. 2017;74(3):363. doi:10.1001/jamaneurol.2016.5908

To the Editor Shahim et al1 reported the finding that individuals with persistent mild traumatic brain injury (mTBI) (postconcussive syndrome) have increased levels of neurofilament light (NF-L) proteins in their spinal fluid that was suggestive of axonal white matter injury. The increase in NF-L proteins correlated with Rivermead Concussion scores and lifetime concussion events.

Research from our laboratory on patients with small-cell cancer of the lung (SCCL) who exhibited visual paraneoplastic syndrome were observed to have elevated levels of antibodies to the light chain neurofilament and several of these patients had antibodies to the medium and heavy neurofilament proteins.2,3 These antibodies to the NF proteins reacted with the small-cell cancer and the large retinal ganglion cells affected by the visual paraneoplasia. The patients with these antibodies survived longer than those patients with SCCL alone. The antineurofilament antibodies resulted in the selective immunoablation of large retinal ganglion cells following injection of these antibodies into cat vitreous.3 These observations on the SCCL population are supportive of the observation that the NF-L proteins seen in mTBI pass from the neuronal compartment into the cerebrospinal fluid over a prolonged period. The continued release may serve as an antigenic stimulus to generate anti-NF antibodies in blood serum. It would be of interest if the patients with mTBI also exhibited elevated levels of anti–NF-L chain, thereby confirming a potential role of these antibodies in neuropathological processes.

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Article Information

Corresponding Author: Steve Kornguth, PhD, Kinesiology and Health Education, The University of Texas at Austin, 2901 San Jacinto Blvd, The University of Texas at Austin, Austin, TX 78712 (steve_kornguth@utexas.edu).

Published Online: January 30, 2017. doi:10.1001/jamaneurol.2016.5908

Conflict of Interest Disclosures: None reported.

Shahim  P, Tegner  Y, Gustafsson  B,  et al.  Neurochemical aftermath of repetitive mild traumatic brain injury.  JAMA Neurol. 2016;73(11):1308-1315.PubMedArticle
Grunwald  GB, Klein  R, Simmonds  MA, Kornguth  SE.  Autoimmune basis for visual paraneoplastic syndrome in patients with small-cell lung carcinoma.  Lancet. 1985;1(8430):658-661.PubMedArticle
Kornguth  SE, Kalinke  T, Grunwald  GB, Schutta  H, Dahl  D.  Anti-neurofilament antibodies in the sera of patients with small cell carcinoma of the lung and with visual paraneoplastic syndrome.  Cancer Res. 1986;46(5):2588-2595.PubMed