Today s topic areas. We Keep Forgetting Our Topic: New Thinking on Concussion Exam and Management

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1 We Keep Forgetting Our Topic: New Thinking on Concussion Exam and Management Stephanie N. Aldret, DO, CAQSM Louisiana Orthopaedic Specialists, Lafayette, LA Team Physician, University of Louisiana at Lafayette President-Elect, Louisiana Osteopathic Medical Association Randy L. Aldret, EdD, ATC, LAT Assistant Professor and Director, Athletic Training Program University of Louisiana at Lafayette Director of Continuing Education, Louisiana Athletic Trainers Association Today s topic areas Acute examination Sidelines and in the office Treatment innovations What is making a difference in our patients What does the science say? The search for the Magic Bullet Next frontiers in research Research for a reason. 1

Today s topic areas Acute examination Sidelines and in the office Treatment innovations What is making a difference in our patients What does the science say?

2 Today s topic areas Acute examination Sidelines and in the office Treatment innovations What is making a difference in our patients What does the science say? The search for the Magic Bullet Next frontiers in research Research for a reason. History Symptoms Neurological Exam Neurocognitive Testing Balance Assessment Exertional Testing Acute Evaluation Our Ragin Cajun spirit goes beyond athletics. 2

3 Clinic Evaluation History Symptom Scale Neurocognitive Testing SCAT3, ImPACT, C3Logix Neurological Exam Balance Assessment Focused Musculoskeletal Exam Osteopathic Exam We re eager to share what we re learning. 3

4 Today s topic areas Acute examination Sidelines and in the office Treatment innovations What is making a difference in our patients What does the science say? The search for the Magic Bullet Next frontiers in research Research for a reason. 4

Progress in Concussion Treatment Education Active Behavioral Management Academic Adjustments/Accomodations/Modifications Targeted Therapies Vestibular Therapy Vision Therapy We re eager to share what

5 Progress in Concussion Treatment Education Active Behavioral Management Academic Adjustments/Accomodations/Modifications Targeted Therapies Vestibular Therapy Vision Therapy We re eager to share what we re learning. Today s topic areas Acute examination Sidelines and in the office Treatment innovations What is making a difference in our patients What does the science say? The search for the Magic Bullet Next frontiers in research Research for a reason. 5

6 We All Want The Magic Bullet Research for a reason. But the reality of exam and care requires buckshot We have a gift of bringing people together. 6

Fragment (SNTF) Axonal injury marker generated by the calpain family of calcium activated proteases Neuro specific Enolase (NSE) Protein highly expressed in the neuronal soma, but also in RBC s

7 The headlines are inadvertently accurate We re eager to share what we re learning. that a single blood biomarker Neurofilament Light (NF L) Intra axonal structural protein in large caliber axons Tau Intra axonal structure protein in thin, unmyelinated axons Spectrin N terminal Fragment (SNTF) Axonal injury marker generated by the calpain family of calcium activated proteases Neuro specific Enolase (NSE) Protein highly expressed in the neuronal soma, but also in RBC s Ubiquitin C terminal hydrolase L1 (UCHL 1) Deubiquitinating enzyme highly expressed in neurons but also in the gonads, lungs S100 Astroglial protein which is CNS enriched but not CNS specific Glial fibrillary acidic protein (GFAP) Astroglial protein which is CNS specific Interleukins (IL family) This is our time, and we re determined to make the most of it. 7

Our Pilot Study Outcomes Some good Both subjects demonstrated a significant spike in IL 6, 8 & 10 in the post 72 hr and 1 week follow up, then returned to near baseline at postseason Best data

8 is not sufficient for diagnosis Our pilot study Professional Hockey So TONS of concussions, right? TONS of turnover 2 great case studies but no generalizable data This is our time, and we re determined to make the most of it. Our Pilot Study Outcomes Some good Both subjects demonstrated a significant spike in IL 6, 8 & 10 in the post 72 hr and 1 week follow up, then returned to near baseline at postseason Best data reinforced what we believed about VOMS: One of the subjects NPC spiked to 12.67cm at the 5 week mark before leveling at 4cm at post season measure (baseline was 3.67cm) Other subject did not spike significantly but saw a large increase (1 to 3.67cm) over the course of the season some not so good We did not run ELISA on SNTF, which has gained some steam recently Siman et al (2015) GFAP, UCH L1, NF L, NF M all had slight increases in the immediate measures post injury, but return to at or near baseline by the post season blood draw Interestingly, we had elevated levels of NF L & NF M at BASELINE, but did not increase significantly over the course of the season If it is detectable in the athletes already, are they damaged already from the trauma of previous season? We re eager to share what we re learning. 8

9 Current Research Confirms This Research does not support diagnosis by blood for now Posti et al. (2016): Px w/ortho trauma & high levels of UCHL1 or GFAP may be falsely diagnosed as having concomitant mtbi Same with Puvenna et al (2012), but could correlate s100, which gives it traction but Babcock et al (2013) found s100 had no ability to predict post concussion syndrome in children tested within 6 hrs post injury Our Ragin Cajun spirit goes beyond athletics. Today s topic areas Acute examination Sidelines and in the office Treatment innovations What is making a difference in our patients What does the science say? The search for the Magic Bullet Next frontiers in research Research for a reason. 9

10 So Where Do We Go From Here?!? Blood, but not just inflammtory markers Exosomes, Genetic markers Baseline/Exam/Rehab with vestibular and oculomotor components Nothing will ever replace a good H&P, but need the baselines More research = normative data Advancing diagnostic into new arenas Sleep as medicine, tying quality to markers, symptoms This is our time, and we re determined to make the most of it. Not your typical blood markers Literature to follow Alzheimer's/HIV E/FT Dementia PINCH me! (treatment) Inhibition of TAU proliferation Claudin 3, 5 (diagnosis) Axonal damage, blood brain barrier Exosome (diagnosis) Neurogranin, GFAP within the exosome not free in blood Will this ever be practical on field or in the clinic?!? Research for a reason. 10

SYNC/Stanford Using VR technology, isolating oculomotor system Specifically dynamic foveation/visuomotor synchronization via predictive timing that accounts for the constraint of the sensorimotor

11 The Eyes Have It Near Point Convergence Statistical power of Near Point Convergence (P <.001) when it extended past 6 cm When combined, NPC, Visual Motion Sensitivity (VMS) & Vestibular Ocular Reflex (hvor) accurately identified a concussion 89% of the time Mucha A et al (2014) EYE SYNC/Stanford Using VR technology, isolating oculomotor system Specifically dynamic foveation/visuomotor synchronization via predictive timing that accounts for the constraint of the sensorimotor processing delay Maruat & Ghajar (2014) We have a gift of bringing people together. Yolk not Shell: Using DTI/fMRI/MRS Alterations in CBF Children yrs, w/src, no other evidence of trauma White Matter/Corpus Callosum Posterior aspect is more vulnerable than the anterior Minimal fiber disruption but multiple regions of fractional anisotropy, specifically in the splenium and mildly in the midbody, and no significant change in the genu Increasing levels of Choline, Creatine with subsequent mtbi Implication for acute diagnosis, monitoring through recovery Do we ever get back to normal? We re eager to share what we re learning. 11

12 Recommendations Maintain a multi faceted approach in all aspects Conduct Baseline Testing, Assessment, Care, R T L/R T P Longitudinal tracking of patients Fleminger (2012): mtbi represents a substantial risk factor for development of Alzheimer s particularly in males and individuals who have a genetic predisposition to the disorder Education with good information This involves a large number of kids, so it involves an even larger number of parents. This is our time, and we re determined to make the most of it. References Giza CC, Hovda DA. The New Neurometabolic Cascade of Concussion. Neurosurgery [Internet] Oct [cited 2017 Apr 11];75(0 4):S Available from: Rutgers DR, Toulgoat F, Cazejust J, Fillard P, Lasjaunias P, Ducreux D. White Matter Abnormalities in Mild Traumatic Brain Injury: A Diffusion Tensor Imaging Study. American Journal of Neuroradiology [Internet] Mar 1 [cited 2017 Apr 11];29(3): Available from: Maugans TA, Farley C, Altaye M, Leach J, Cecil KM. Pediatric Sports Related Concussion Produces Cerebral Blood Flow Alterations. Pediatrics [Internet] Jan 1 [cited 2017 Apr 11];129(1): Available from: Doherty CP, O Keefe E, Wallace E, Loftus T, Keaney J, Kealy J, et al. Blood Brain Barrier Dysfunction as a Hallmark Pathology in Chronic Traumatic Encephalopathy. J Neuropathol Exp Neurol Jul;75(7): Johnson B, Gay M, Zhang K, Neuburger T, Horovitz S, Hallett M, Sebastianelli W, Slobounov S. The Use of Magnetic Resonance Spectroscopy in the Subacute Evaluation of Athletes Recovering from Single and Multiple Mile Traumatic Brain Injury. J of Neurotrauma Aug; 29(13): Available from: Posti JP, Hossain I, Takala RSK, Liedes H, Newcombe V, Outtrim J, et al. Glial Fibrillary Acidic Protein and Ubiquitin C Terminal Hydrolase L1 Are Not Specific Biomarkers for Mild CT Negative Traumatic Brain Injury. J Neurotrauma Jan 27; Roozenbeek B, Maas AIR, Menon DK. Changing patterns in the epidemiology of traumatic brain injury. Nat Rev Neurol ;9(4): Shetty T, Raince A, Manning E, Tsiouris AJ. Imaging in Chronic Traumatic Encephalopathy and Traumatic Brain Injury. Sports Health [Internet] Jan 1 [cited 2017 Apr 13];8(1): Available from: 12

13 References GBabcock L, Byczkowski T, Wade SL, Ho M, Bazarian JJ. Inability of S100B to Predict Post Concussion Syndrome in Children who Present to the Emergency Department with Mild Traumatic Brain Injury: A Brief Report. Pediatr Emerg Care [Internet] Apr [cited 2017 Apr 11];29(4): Available from: Puvenna V, Brennan C, Shaw G, Yang C, Marchi N, Bazarian JJ, et al. Significance of Ubiquitin Carboxy Terminal Hydrolase L1 Elevations in Athletes after Sub Concussive Head Hits. PLOS ONE [Internet] May 7 [cited 2017 Apr 11];9(5):e Available from: LaDuca H, Farwell KD, Vuong H, Lu H M, Mu W, Shahmirzadi L, et al. Exome sequencing covers >98% of mutations identified on targeted next generation sequencing panels. PLOS ONE [Internet] Feb 2 [cited 2017 Apr 12];12(2):e Available from: Ozdemir AY, Rom I, Kovalevich J, Yen W, Adiga R, Dave RS, et al. PINCH in the Cellular Stress Response to Tau Hyperphosphorylation. PLOS ONE [Internet] Mar 12 [cited 2017 Apr 12];8(3):e Available from: Maruta J, Ghajar J. Detecting Eye Movement Abnormalities from Concussion [cited 2017 Apr 13];28: Available from: Siman R, Shahim P, Tegner Y, Blennow K, Zetterberg H, Smith DH. Serum SNTF Increases in Concussed Professional Ice Hockey Players and Relates to the Severity of Postconcussion Symptoms. Journal of Neurotrauma [Internet] Nov 24 [cited 2017 Apr 13];32(17): Aoki Y, Inokuchi R, Gunshin M, Yahagi N, Suwa H. Diffusion tensor imaging studies of mild traumatic brain injury: a meta analysis. J Neurol Neurosurg Psychiatry [Internet] Sep 1 [cited 2017 Apr 13];83(9): Johnson B, Zhang K, Gay M, Neuberger T, Horovitz S, Hallett M, et al. Metabolic alterations in corpus callosum may compromise brain functional connectivity in MTBI patients: An 1H MRS study. Neuroscience Letters [Internet] Feb 10 [cited 2017 Apr 13];509(1):5 8. Any Questions? snaldret@gmail.com raldret@louisiana.edu 13

14 Thank You For Having Us Back In Oklahoma! 14

Blood Biomarkers for Brain Injury. Dianne Langford Associate Professor Department of Neuroscience Lewis Katz School of Medicine at Temple University

Blood Biomarkers for Brain Injury Dianne Langford Associate Professor Department of Neuroscience Lewis Katz School of Medicine at Temple University TOPICS COVERED What are we measuring? How do markers