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Pathophysiology ofConcussions
November 9, 2013
Jon Schultz, MDUMKC Sports Medicine Kansas City, Missouri
Learning Objectives
• Appreciate the historical progression of concussion research
• Recognize the impact of concussions on today’s society
• Describe our current understanding of concussive pathophysiology
So what’s the big deal???
• “Compared to the complexity of a brain, a galaxy is just an inert lump” physicist Sir Roger Penrose
• “Concussion is considered to be among the most complex injuries in sport medicine to diagnose, assess, and manage” McCrory et al, Consensus Statement on Concussion in Sport, Clin J Sport Med Volume 23, Number 2, March 2013
• Limited research abilities
• ED visits for sports-related TBI has risen over the past 10 years
• Post-concussive syndrome, malignant cerebral edema, & second impact syndrome
• Worries of chronic traumatic encephalopathy and dementia in retired NFL players
“DINGS” MATTER
AJSM, Lovell et al (2004)
43 HS athletes with “Grade 1” concussion
Neuropsych testing 36 hrs after concussion
Statistically significant differences in memory and symptoms
compared to baseline
Conclusion: Old standard RTP guidelines may be too liberal
MECHANISM OF INJURY
Rotational (angular) acceleration: diffuse shearing forces deep in brain causing axonal injury
Translational (linear) acceleration: tensile (pulling apart) and compressive forces resulting in focal brain injury
Rotational Linear
Pathophysiology of concussion“neurometabolic cascade”
Nuerotramsmitter release with massive depolarization of neurons along with axonal stretch inury
Ionic disruption
Metabolic disruption
Energy supply and demand mismatch
Decreased cerebral blood
flow
Mitochondrial dysfunction
Increased inflammation and axonal swelling
Neurotransmission disruption Window of vulnerability
Giza and DiFioriPathophysiology of Sports-Related Concussion: An Update on Basic Science and Translational Research Jan • Feb 2011 SPORTS HEALTH
Lateral fluid percussion for inducing a concussion in the lab
concussion video.htm
Ionic and metabolic dysfunction
Cerebral microdialysis measured elevated levels of glutamate and potassium in head-injured patients in the ICU. J Neurosurg.1998;89:507-518, 971-982.
Components of clinical MD catheter. 1, pump connector; 2, inlet tube; 3, MD catheter; 4, MD membrane; 5, outlet tube; 6, microvial holder; 7, microvial for collection of microdialysate.
Tisdall M M , and Smith M Br. J. Anaesth. 2006;97:18-25
© The Board of Management and Trustees of the British Journal of Anaesthesia 2006. All rights reserved. For Permissions, please e-mail: [email protected]
Chefer V, Thompson A, Zapata A and Shippenberg T
Overview of Brain Microdialysis
Curr Protoc Neurosci. 2009 April
Schematic representation of MD catheter in brain tissue.
Tisdall M M , and Smith M Br. J. Anaesth. 2006;97:18-25
© The Board of Management and Trustees of the British Journal of Anaesthesia 2006. All rights reserved. For Permissions, please e-mail: [email protected]
Matthew F. Grady, MD, et al, Pediatric Annals, September 2012 - Volume 41 · Issue 9
Na+ influx
pH↑↓
Changes in LPR in ‘at-risk’ (a) and normal (b) brain during a period of low and normal CPP. The normal range for LPR is shown by the shaded area.
Tisdall M M , and Smith M Br. J. Anaesth. 2006;97:18-25
© The Board of Management and Trustees of the British Journal of Anaesthesia 2006. All rights reserved. For Permissions, please e-mail: [email protected]
Human evidence
• After human TBI, positron emission tomography (PET) scanning has shown a similar pattern of early hyperglycolysis followed by glucose metabolic depression. J Head Trauma Rehabil. 2001;16:135-148, J Neurosurg. 1997;86:241-251.
• Profound glucose metabolic depression was seen after mild TBI, to the same degree as severe TBI. J Neurotrauma. 2000;17:389-401.
• Metabolic recovery generally takes weeks to months after moderate to severe TBI. J Head Trauma Rehabil. 2001;16:135-148.
Pathophysiology of concussion“neurometabolic cascade”
Neurotramsmitter release due to massive depolarization of neurons and axonal stretch inury
Ionic disrup
tion
Energy supply and demand mismatch
Decreased
cerebral blood
flow
Increased inflammation and axonal swelling
Neurotransmission disruption
Giza and DiFioriPathophysiology of Sports-Related Concussion: An Update on Basic Science and Translational Research Jan • Feb 2011 SPORTS HEALTH
So now what do we do???
Good legs
Forced overuse within the first week of experimental injury actually worsened the animal’s recovery, causing greater cell death in the brain and hampering neurologic recovery. Exp Neurol.1999;157:349-358. Brain Res. 1998;783:286-292. J Neurosci. 1996;16:4776-4786.
Motorcortex
Delay forced overuse
Delay overuse by 1 week, and neurologic recovery was more complete. But the amount of cell death was not affected. Brain Res.1991;561:106-119.
Voluntary exercise
If the animal runs within 1 week of a mild injury, BDNF levels do not increase and cognitive performance suffers. Neuroscience. 2004;125:129-139.
BDNF = brain-derived neurotrophic factor
What we know in the rat post-injury
• Period of vulnerability to premature activation = known abnormal metabolic state after experimental TBI = 7 to 10 days. Brain Res. 1991;561:106-119.
• A 2nd TBI within 3 to 5 days after the first = impaired cognitive function but not when the second injury was applied at 7 days. Neurosurgery. 2005;56:364-374.
Does this apply to humans?
It appears so…
95 student-athletes (80 males, 15 females: age = 15.88 +/- 1.35 years) with “moderate” postconcussive activity fared the best on neurocognitive testing. The higher and the lower activity levels were associated with the worst scores. J Athl Train.2008;43:265-274.
College football players
• With a history of concussion were 3.4 times more likely to suffer a concussion that season.
• 6.5% of football players had a repeat injury in the same season
• 75% (9 of 12) had a recurrent injury within 7 days of the first injury, and 11 of 12 recurred within 10 days.
• The risk for repeat injury appears to be greatest within 10 days following the initial concussion.Guskiewicz KM, McCrea M, Marshall SW, et al. Cumulative effects associatedwith recurrent concussion in collegiate football players: the NCAAconcussion study. JAMA. 2003;290:2549-2555
Rats and CTE
• Molecular markers associated with dementing processes
• Alzheimer disease is characterized by accumulation of tau and amyloid β (Aβ) protein
• Rodents do not readily develop Aβ plaques• Apolipoprotein (Apo) E4 allele may be a
genetic marker making certain individuals more susceptible to dementia
SYMPTOMS OF CONCUSSIONS
Headache Nausea Balance problems/dizziness Fatigue Drowsiness Feeling “in a fog” Difficulty concentrating Difficulty remembering Sensitivity to light Sensitivity to noise Blurred vision Feeling slowed down
Randolph, et.al. Arch. Clin. Neuropsychol. 2009
RETURN TO PLAY ISSUESA player with diagnosed concussion should not be allowed
to return to play on the day of injury.
Occasionally, in adult athletes, return to play on the same day as the injury may be allowed.