In Reply We thank Kornguth for the comment on our article1 on hockey players with persistent symptoms after repetitive mild traumatic brain injury. We showed that a proportion of players have high cerebrospinal fluid levels of neurofilament light protein (NF-L) indicating ongoing axonal injury.1 We found the discovery of autoantibodies to NF-L in the serum of patients with small-cell lung carcinoma associated visual paraneoplastic syndrome intriguing.2 Interestingly, anti-NF antibodies reacting with axons have also been demonstrated in patients with amyotrophic lateral sclerosis, suggesting a possible autoimmune process.3
As suggested by Kornguth, NF-L passes from the brain to the cerebrospinal fluid, and to blood, over a prolonged period (weeks to months), with higher blood levels predicting worse clinical outcome.4 Whether such a release of potential autoantigens to the bloodstream may generate an autoimmune response in traumatic brain injury cases is currently unknown. Perivascular accumulation of phosphorylated tau aggregates in neurons and astrocytes in the depths of cortical sulci is the defining lesion in chronic traumatic encephalopathy5 (ie, the chronic neurodegenerative disorder found in contact sport athletes with repeated concussions and soldiers exposed to blasts). However, it is not known which type of pathophysiology initiates or drives the progressive neurodegenerative process after the initiating repeated brain injuries.6 Thus, we need to explore multiple possible pathophysiological pathways for the development of both persistent symptoms and chronic neurodegeneration after repetitive mild traumatic brain injuries. In this context, a possible role of autoantibodies to brain antigens, such as NF-L released to the bloodstream in the acute phase and during a prolonged period following trauma, is clearly worth studying.
Corresponding Author: Kaj Blennow, MD, PhD, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, SE-43180 Mölndal, Sweden (firstname.lastname@example.org).
Published Online: January 30, 2017. doi:10.1001/jamaneurol.2016.5905
Conflict of Interest Disclosures: Drs Zetterberg and Blennow are cofounders of Brain Biomarker Solutions in Gothenburg AB, a University of Gothenburg venture-based platform company at the University of Gothenburg. No other disclosures were reported.
Shahim P, Zetterberg H, Blennow K. Neurofilament Protein and Antineurofilament Antibodies Following Traumatic Brain Injury—Reply. JAMA Neurol. 2017;74(3):363-364. doi:10.1001/jamaneurol.2016.5905