Concussion: Research Overview
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1 Concussion: Research Overview September 30, 2013 Hugh J.L. Garton, M.D.,M.HSc. Dept. of Neurosurgery University of Michigan
2 No Disclosures
3 Overview Anatomy / Definitions Biomechanics Cerebral Blood Flow Blood Brain Barrier Disruption Neuroinflammation
4
5
6 Intracranial Compensation for Expanding Mass Venous Blood Arterial Blood Brain CSF Normal State ICP Normal VB AB Brain MASS CSF Compensated State ICP Normal VB AB Brain MASS Uncompensated State ICP Elevated
7 Pressure-Volume Relationship ICP Compensation Volume of Enlarging Mass Critical Mass Size
8 Cerebral Autoregulation CBF Mean Arterial Pressure
9 Blood Brain Barrier Picture Credit:
10 Biomechanics How much force does it take? Where does the force go? How likely is the to produce concussion?
11 Helmet Studies: Forbes et al.
12 3% of all collisions have TA > than mean with concussion 0.02% of all collisions result in concussion. Odds of concussion with sufficient force are 1:150
13 Pressure Pressure Distribution Force Distribution after impact Note Occipital pressure spike after frontal impact Time
14 Rotational Forces Silicone Gel Brain Model Element Displacement Aldman, 1981
15 Finite Element Analysis of Concussions in 22 NFL player Viano et al, 2005 (Wayne State HIM) Largest Strains Fornix Midbrain Corpus Callosum Strain correlated with return to play
16
17 Membrane injury Ion Leak (K+) Glutamate Release NMDA Receptor Activation Ca++ influx Mitochondrial Dysfunction Increase ATP demands Glycolytic Energy Pathway Acidosis Membrane Permiabilty
18 DTI - Imaging Evidence Diffusion Tensor Imaging Adults Consistent with Axonal dysfunction Pediatrics Conflicting Results. J. Neurosci., December 12, (50):
19 MRS Imaging N-Acetyl Aspartate Vagnozzi et al. Brain, pts SRC vs. 30 healthy controls Scans at 3, 15, 22, 30 days
20 Vascular Pathology in mtbi Cerebral Blood Flow Transcranial doppler studies Early reduction in MCA velocity Variable results in children. Autoregulation More passive/pressure dependent Cerebrovascular Reactivity Reduced after mtbi Clin Physiol Funct Imaging (2011) 31, pp85 93
21 Adult vs. Pediatric Anatomic Injury by MRI/ DTI NAA: Cr Ratio Cerebral Blood Flow Adult Demonstrated Depressed from 3-15 days from injury Pediatric More difficulty to find. Less Apparent Depressed with delayed recovery Depressed with delayed recovery BUT Hyperemia more common Evaluation of patients with sports related concussion as determined by IMPACT and other validated Clinical concussion measures Vagnozzi et al, 2010 Maugans et al, 2012
22 Pediatric CBF Maugans, PEDIATRICS Volume 129, Number 1, January 2012
23 Second Impact Syndrome J Neurosurg Pediatrics 11: , 2013
24 Blood Brain Barrier Korn et al, pts Post Concussive Syndrome Focal localized neocortical EEG slowing 83% Regional hypoperfusion, 73% BBB disruption Journal of Clinical Neurophysiology Volume 22, Number 1, February 2005
25 Neuroinflammation Journal of Cerebral Blood Flow & Metabolism (2012) 32,
26 Inflammatory Agents Interleukin 1 (IL-1) IL-1 α Rapid spike after concussion IL-1 β Slow Rise, delayed return May promote regenerative growth factor secretion Blockade reduces tissue edema in animal models Tumor Necrosis Factor α (TNF α) Peaks within hours of trauma Role in BBB permeabilty IL-6 Transforming Growth Factor β (TGF- β) IL -10
27 Inflammation- Mixed Picture Prolonged experimental exposure to inflammatory cytokines produces additional tissue injury?? Experimental elimination of neuroinflammatory response produced additional tissue injury
28 No benefit to NSAIDS Ibuprofen: Chronic treatment worsens outcome in experimental TBI Minocycline: Reduces apoptosis, no functional benefit HU-211 (anti TNF- α): No benefit in human trials
29 Conclusions Current research identified pathophysiological correlates of clinical concussion Pathophysiological changes occur rapidly after injury and may prove long lasting Clinical recovery may precede normalization of physiological parameters
30 Well understood biomechanical forces only variably produced concussion?patient factors.? Injury Minutia Cerebral Vascular abnormalities support window of vulnerability after injury Immunological changes after injury may provide opportunities for intervention but limited by uncertain specificity and timing
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