concussions and biomarkers · overview • concussions – background – recognition – recovery...
TRANSCRIPT
Concussions and Biomarkers
Stephanie F. Alessi-LaRosa, MD, MPHAssociate Director of HHC Sports Neurology Program
March 20, 2020
Disclosures
• No relevant financial or nonfinancial relationships exist
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Overview
• Concussions– Background– Recognition– Recovery
• Biomarkers– Imaging– Fluid– Limitations– Future directions
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Concussion Definition
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• A transient, complex pathophysiologic response to biomechanical forces imparted to the brain, resulting in onset of neurologic symptoms that predominantly reflect a functional disturbance, rather than a gross structural injury.
– Distinction of sports-related concussion: implicit assumption that the athlete will purposely be returning to contact risk (vs. MVA-related etc)
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• Brain in the skull with CSF like an egg in a glass with water – if shaken, the brain can strike the skull
• Axons run in groups from brain to brainstem to cord like string cheese –rotational or whiplash injuries can stretch/shear them
“Network” Injury
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INJU
RY
TIME
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• Possible: In a list, concussion is not most likely– Common mimickers: dehydration, viral
illness, migraines, hyperthermia
• Probable: In a list, concussion is most likely
• Definite: Concussion is only explanation
Treat as Concussed
Situational Treatment
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• Based on:– Mechanism – Not every hit to the head is a concussion
– Symptom course – first 24-48 hours•Ex: Headache resolved in 12 hrs and no further symptoms
•Ex: Headache with migraine features, sleep issues, persistent nausea/change in appetite, dizziness –lasting longer than 24 hours
Mechanisms
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Mechanisms
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NFL~ 1,800
COLLEGE FOOTBALL~ 73,660
HIGH SCHOOL FOOTBALL~ 1,100,000
YOUTH FOOTBALL ~ 2,800,000
YOUTH SOCCER ~ 3,000,000YOUTH ICE HOCKEY >500,000
Research being done here
Most of the players here
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– Mental status•How did you get injured?•What was last play?•What is the current score?•Which team did you play last game?
– Pupil exam– VOMS testing*– Coordination/balance testing
•Finger-to-nose•Tandem gait forward and reverse•Single leg stance + squat
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• Smooth pursuits• Saccades:
– Horizontal– Vertical
• Convergence• VOR
– Horizontal– Vertical
• Visual motion sensitivity test
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•The brain likes:
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• As a principle, use the fewest prescription medications and maximize lifestyle changes– Use lowest effective dose possible
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• Avoid Avoidance!– Activity/light/sound etc.
•Leads to prolonged recovery/difficulty when reintroduced
– Ex: Wearing sunglasses indoors– Ex: No physical activity for a week
After first 48 hours, can always do something!
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• After initial injury is healed, symptoms persist for other reasons
• NOT a “long concussion” but is a separate, complex disorder
• Requires a different approach:
DEPRESSION/ANXIETY
SLEEP DISTURBANCE
HEADACHES
MEMORY CHANGES
CONCENTRATION ISSUES
Traumatic Brain injury and biomarkers
• TBIs are heterogeneous conditions• Unable to manage different patients with the identical treatment• Biomarkers may help identify subsets for specific treatment and
prognosis• A more objective tool for assessing presence/severity of
concussion
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Biomarkers• Imaging
– fMRI– MR Spectroscopy– DTI
• Serum/plasma– GFAP plasma– Tau plasma
• Saliva• CSF• EEG/qEEG• Urine
– NMR Spectroscopy - prognosis
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Imaging
• First neuroimaging and then treatment based on these results personalized approach
• 76 studies reviewed: Moderate risk of bias from lack of generalizability and inclusion of limited age ranges/male athletes/small sample sizes
• What is DTI?
• DTI: decreased mean diffusivity and/or increased fractional anisotropy in WM w/i 6 mos post injury
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Functional MRI (fMRI)
• What is fMRI?
• If typical MRI shows structural white matter integrity, fMRI would show success of treatment from transcranial brain stimulation
• Variable results. Looked at working memory +/- activity in task-related networks. Activity outside of core regions with tasks after concussion.
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MR Spectroscopy – dopamine transporters
• What is MR spectroscopy?
• May predict patients who would benefit from cognitive-enhancing therapy
• relative decreased NAA in WM acutely and subsequent recovery – also studies with chronically decreased NAA
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Urine NMR spectroscopy
• What is NMR spectroscopy?
• Experimental • Within 72 hours of injury identified 5 different metabolites
altered compared to pre-concussion.
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• What is EEG/qEEG?
• At rest or during tasks – electrographic changes compared to baseline– qEEG: severity of injury
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GFAP
• What is GFAP?
• Detect TBI early on with MRI positive findings (not mild TBI/concussion)
• Diagnostic not prognostic
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Tau
• What is tau?
• Acute and chronic TBI• Diagnostic and prognostic
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Salivary cortisol
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Fluid biomarkers
• Serum/plasma: AMPAR, S100 calcium binding protein, tau, GFAP, NSE
• CSF: decreased amyloid-beta-42 and increased neurofilamentlight – athletes with PCS (sx >1 year)
• Moderate to high bias risk: limited external validity and poor generalizability males/age/sport/sample size small, no controls
• More helpful in understanding pathophysiology of concussion in humans than actually useful clinically.
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Other related areas of research
• Genetics in TBI – predicting risk of injury, prolonged recovery, long-term brain health problems from repetitive head impacts in athletes.
• Can alter outcome by:– Modulating force of neurotrauma and injury extent– Repair mechanisms trajectory of recovery and outcome– Preinjury traits – cognitive reserve etc– Genetic vulnerability to mood disorders and neurotrauma
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Take-Home Points
• Biomarkers require further research to determine ultimate utility in the clinical setting
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Thank You!
Stephanie F. Alessi-LaRosa, MD, MPHAssociate Director of HHC Sports Neurology Program
Website: hartfordhealthcare.org/sportsneuroOffice number: (860) 524-4330
Questions? Comments?
@SAlessiLaRosa
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• Eckner, JT, YK Oh, et al. Effect of neck muscle strength and anticipatory cervical muscle activation on the kinematic response of the head to impulsive loads. Am J Sports Med 42(3):566-576, 2014.
• Thomas D, et al. Benefits of strict rest after acute concussion: A Randomized Control Trial. Pediatrics 135(2) 213-226, 2016.
• Harmon, K, et al. American Medical Society for Sports Medicine Position Statement: Concussion in Sport. Clinical Journal of Sport Medicine 23(1) 1-8, 2013.
• Mucha et al. A Brief Vestibular/Ocular Motor Screening (VOMS) Assessment to Evaluate Concussions: Preliminary Findings. American Journal of Sports Medicine 42(10), 2014.
• Leddy J et al. Early Subthreshold Aerobic Exercise for Sport-Related Concussion A Randomized Control Trial. Feb 2019.
• Feng, J. Traumatic brain injury in 2019: databases, biomarkers, and stratified treatment. Lancet Neurology (19) 7-9. Jan 2020.
• Papa, L. Potential Blood-Based Biomarkers for Concussion. Sports Med Arthrosc. 2016; 24(3):108-115.• Asken, B. Concussion Biomarkers: Deviating From the Garden Path. JAMA Neurol. 2019;76(5):515-516.• McCrea, M. et al. Role of advanced neuroimaging, fluid biomarkers and genetic testing in the
assessment of sport-related concussion: a systematic review. Br J Sports Med. 51 (12), 919-929, 2017.• Paxman, E. Et al. Metabolomic biomarkers of concussion. Br J Sports Med. 51(11), 2017.