Neurochemical Aftermath of Repetitive Mild Traumatic Brain Injury

IMPORTANCE: Evidence is accumulating that repeated mild traumatic brain injury (mTBI) incidents can lead to persistent, long-term debilitating symptoms and in some cases a progressive neurodegenerative condition referred to as chronic traumatic encephalopathy. However, to our knowledge, there are no objective tools to examine to which degree persistent symptoms after mTBI are caused by neuronal injury. OBJECTIVE: To determine whether persistent symptoms after mTBI are associated with brain injury as evaluated by cerebrospinal fluid biochemical markers for axonal damage and other aspects of central nervous system injury. DESIGN, SETTINGS, AND PARTICIPANTS: A multicenter cross-sectional study involving professional Swedish ice hockey players who have had repeated mTBI, had postconcussion symptoms for more than 3 months, and fulfilled the criteria for postconcussion syndrome (PCS) according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) matched with neurologically healthy control individuals. The participants were enrolled between January 2014 and February 2016. The players were also assessed with Rivermead Post Concussion Symptoms Questionnaire and magnetic resonance imaging. MAIN OUTCOMES AND MEASURES: Neurofilament light protein, total tau, glial fibrillary acidic protein, amyloid β, phosphorylated tau, and neurogranin concentrations in cerebrospinal fluid. RESULTS: A total of 31 participants (16 men with PCS; median age, 31 years; range, 22-53 years; and 15 control individuals [11 men and 4 women]; median age, 25 years; range, 21-35 years) were assessed. Of 16 players with PCS, 9 had PCS symptoms for more than 1 year, while the remaining 7 returned to play within a year. Neurofilament light proteins were significantly increased in players with PCS for more than 1 year (median, 410 pg/mL; range, 230-1440 pg/mL) compared with players whose PCS resolved within 1 year (median, 210 pg/mL; range, 140-460 pg/mL) as well as control individuals (median 238 pg/mL, range 128-526 pg/mL; P = .04 and P = .02, respectively). Furthermore, neurofilament light protein concentrations correlated with Rivermead Post Concussion Symptoms Questionnaire scores and lifetime concussion events (ρ = 0.58, P = .02 and ρ = 0.52, P = .04, respectively). Overall, players with PCS had significantly lower cerebrospinal fluid amyloid-β levels compared with control individuals (median, 1094 pg/mL; range, 845-1305 pg/mL; P = .05). CONCLUSIONS AND RELEVANCE: Increased cerebrospinal fluid neurofilament light proteins and reduced amyloid β were observed in patients with PCS, suggestive of axonal white matter injury and amyloid deposition. Measurement of these biomarkers may be an objective tool to assess the degree of central nervous system injury in individuals with PCS and to distinguish individuals who are at risk of developing chronic traumatic encephalopathy

Sleep deprivation and cerebrospinal fluid biomarkers for Alzheimer's disease

Study Objectives: To investigate the cumulative effect of five consecutive nights of partial sleep deprivation (PSD) on a panel of cerebrospinal fluid (CSF) biomarkers in healthy adults. Methods: A randomized, cross-over study conducted at the University of Gothenburg. The participants (N = 13) were healthy adults (20–40 years of age) with a normal sleeping pattern. The participants underwent a baseline sleep period consisting of five nights with 8 hr spent in bed. A subsequent period with PSD consisted of five nights of maximum 4 hr of sleep per night. Four participants were also subjected to a prolonged period of PSD consisting of eight nights with 4 hr of sleep per night. Sleep was monitored by means of observation, actigraphy, and continuous polysomnographic recordings. CSF samples were collected by routine lumbar puncture after each period. CSF biomarkers included the 38, 40, and 42 amino acid–long Aβ isoforms, total-τ, phospho-τ, orexin, monoamine metabolites (3-methoxy-4-hydroxyphenylglycol, homovanillinic acid, and 5-hydroxyindoleacetic acid), neuron-derived biomarkers (neurofilament light, neuron-specific enolase, and fatty acid–binding protein), and astro- and microglia-derived biomarkers (glial fibrillary acidic protein, S-100B, and YKL-40). Results: PSD was associated with a 27 per cent increase in CSF orexin concentrations (p = 0.001). No PSD-related changes in CSF biomarkers for amyloid build-up in the brain, Alzheimer’s disease (AD)-type neurodegeneration, or astroglial activation were observed. PSD led to a shortening of time spent in all sleep stages except slow-wave sleep (SWS). Conclusion: Five to eight consecutive nights of PSD, with preserved SWS, increased CSF orexin but had no effect on CSF biomarkers for amyloid deposition, neuronal injury, and astroglial activation