Concussion – Challenges, Treatment, and the Future Michel Rathbone M.B., Ch.B., PhD, FRCPC (NEUROLOGY) Professor Medicine (Division of Neurology) McMaster University

Conflicts of Interest Financial conflicts of interest Neurology consultant to ABI and Concussion clinics Provide expert medical legal evidence CEO of Libramen Naturals Inc. Non financial conflicts of interest None Unapproved drug use disclosure

Collaborators TRI Dinesh Kumbhare Queens University PMR Alasdair Rathbone McMaster University Pediatrics Surejini Tharmardinam McMaster University Kinesiology Mitchell Locke Aimee Nelson McMaster University Rehabilitation Science William Parkinson Rathbone Group Pamela Middlemiss (Study coordinator) Teresa Gambale (Research Nurse) Shazia Malik Shaji Khan Adrienne Atayde Rosemary Nam Sabrina Campbell Rahim Ahmed Tegveer Kamra Jennifer Guan Ling Yang Angela Dong Radhika Khanna

Concussion – Challenges, Treatment and the Future What are we dealing with? What is concussion?

Trauma induced alteration in mental status Mild Traumatic Brain Injury

American Congress of Rehabilitation Medicine Traumatically induced physiological disruption of brain function described by: 1.Any period of loss of consciousness (after impact) 2.Any loss of memory immediately before/after 3.Mental state alteration at time of incident (dazed, disoriented, confused)

Concussion – Challenges, Treatment and the Future A concussion involves: Mechanical forces Acute biochemical cascade Subsequent repair processes including inflammatory cells

Concussion – Challenges, Treatment and the Future We do not treat concussion We treat the sequelae ‘postconcussion syndrome’

Concussion – Challenges, Treatment and the Future Shakespeare Henry IV Part I – Falstaff What is ‘post concussion syndrome’? A word. What is in that word? Air. A trim reckoning

Post-Concussion Syndrome

THE GREAT RAILWAY MYSTERY 1867-2015 IS PCS DUE TO PSYCHOSOCIAL ISSUES?... OR…. IS PCS DUE TO ORGANIC CHANGES IN BRAIN?

Risk factors for MHI and post-concussive syndrome Substance abuse (especially alcohol) Lower socio-economic status Overcrowded areas History of psychiatric problems, learning disabilities, relationship difficulties Past head injury Migraine/headache or other Pain Condition High symptom reporting

PCS – Structural ? Better technology improving identification of changes Do visualized brain changes represent brain damage or altered psychological function? Will SPECT or fMRI images alter treatment?

J. Neurol. Neurosurg. Psychiatry 2008;79;300-306 Mild traumatic brain injury does not predict acute postconcussion syndrome S Meares, E A Shores, A J Taylor, J Batchelor, R A Bryant, I J Baguley

Post Concussion Syndrome Dizziness ? Headache IL-10 TNF-ɑ IL-1β Irritability IL-6 Post Concussion Syndrome Reduced tolerance IL-1β IL-6 TNF-ɑ Fatigue IL-6 TNF-ɑ IFN-ɣ Personality Changes IL-1β TNF-ɑ IL-6 Cognitive Difficulties IL-1β IL-2 IL-6 TNF-ɑ IFN-ɣ Depression/Anxiety IL-1β IL-2 IL-6 TNF-ɑ Sleep disturbances IL-1β IL-4 IL-6 IL-10

THE GREAT RAILWAY MYSTERY RESOLUTION PSYCHOSOCIAL, ENVIRONMENTAL, AND ORGANIC ISSUES LINKED VIA INFLAMMATORY MECHANISMS

Have all patients that present to a concussion clinic truly sustained a concussion?

American Congress of Rehabilitation Medicine Traumatically induced physiological disruption of brain function described by: 1.Any period of loss of consciousness (after impact) 2.Any loss of memory immediately before/after 3.Mental state alteration at time of incident (dazed, disoriented, confused)

According to the ACRM Criteria 2/3 Concussed 1/3 NOT concussed ? SYMPTOMATOLOGY ? Are there differences in symptomatology?

If the brain is injured - logic predicts cognitive and behavioural consequences

Symptoms Physical Behavioural Cognitive Affective

Frequency (%) Emotional/ Affective Other Physical Dizziness/ Balance No significance between symptom groups yet again, different sample sizes Emotional/ Affective Other Physical Dizziness/ Balance Cognitive Personality/ Behavioural Headache Pain Fatigue Sensory Sleep Symptom Groupings

Concussion No Concussion 1 Cognitive 78.4% Headache 86.7% 2 Headache 75.7% Sensory 80.0% 3 Sensory 67.6% Dizziness 66.7%

Concussion – Challenges, Treatment and the Future More questions Improve treatment

DIZZINESS Mechanical Vestibular? Imaging? Imaging? Central? Measurement? Central? Mal de debarquement

Concussion – Challenges, Treatment and the Future Exercise HIIT vs Endurance Outdoors? Why? In the woods? Why?

Concussion – Challenges, Treatment and the Future Explore the symptoms ‘Environment and Psychosocial’ Do visualized brain changes represent brain damage or altered psychological function? Imaging – may be abnormal before concussion

Concussion – Challenges, Treatment and the Future Explore the symptoms CHRONIC CHANGES Changes in brain circuits and transmitters Do identified brain changes represent brain damage or altered psychological function? May indicate novel pharmacological therapy

Study: Investigating Brain Function in Post-Concussion Syndrome Who: Patients diagnosed with post-concussion syndrome, age 18-50 Commitment: One visit, ~3 hours (*Participants will be compensated*) Contact Us: Investigator: Mitchell Locke lockemb@mcmaster.ca Neurolab, McMaster University: http://mackin.mcmaster.ca/neuro/ Research being conducted at McMaster University to better understand the long-term changes in brain function associated with Post-concussion syndrome. For this important research, we are currently looking for patients with PCS to participate in this research. If you or someone you know may be interested in participating in this research, please contact us at the following e-mail and for more information about the technology used in the NeuroLab, please visit the link provided. IMAGE on right: 2 students from the NeuroLab at McMaster University demonstrating the basic set-up of TMS, whereby a coil held over the participants head is used to non-invasively activate neurons directly below the coil. From this, we can record muscle responses to infer how neurons in the motor area of the brain are communicating.

Concussion – the Future Early treatment of PCS Will that reduce PCS? Identify those likely to have PCS Novel treatment strategy – reduce brain inflammation – study commencing

Concussion – Challenges Late presentation Mixed population Funding for proven symptomatic therapy Resources

Concussion – Challenges, Treatment, and the Future Michel Rathbone M.B., Ch.B., PhD, FRCPC (NEUROLOGY) Professor Medicine (Division of Neurology) McMaster University