Sport Related Concussion Research
The long-term goal of my sport related concussion research is to determine optimal treatment for acute sport related concussion and to understand the long-term consequences of sport related concussion.
Serum Biomarkers: A Path To An Objective Concussion Diagnosis.
The objective of this study is to determine the accuracy of blood biomarkers for diagnosing sports-related concussion and for predicting the duration of post-concussive symptoms. We are enrolling matriculated student athletes at the University of Michigan and at Eastern Michigan University. Pre-season blood samples will be obtained from all athletes participating in high risk contact sports and from control athletes participating in non-contact sports. Additionally, in concussed athletes, blood samples will be obtained after a concussion event. Samples will also be obtained in concussed athletes at 24 to 48 hours after injury and at 2 weeks post-injury. Additionally, blood samples will be obtained from contact-sports athletes without concussion (contact-sports controls) after a game and at 24-48 hours and 2 weeks after the initial draw. Similarly, blood samples will be obtained from athletes participating in non-contact sports (non-contact sport controls) after a game and at 24-48 hours and 2 weeks (+/-3 days) after the initial draw. Blood biomarkers of brain injury will be measured in these samples. Concussed athletes will be examined for resolution of symptoms and return to play. Data from this study will be used to determine the accuracy of blood biomarkers for diagnosing concussion and for predicting the duration of post-concussive symptoms.
Effects of Early Vestibular Rehabilitation Compared to Standard Care in Patients with Dizziness and Balance Disorders after Sport and Recreation Concussion.
The purpose of this study is to examine the effect of early vestibular rehabilitation on reducing dizziness, improving balance, and improving the timeline to achieve medical clearance to return to activities such as sports and work activities, when compared to standard care. The findings of this study are expected to provide medical and sports related professionals with appropriate concussion treatment strategies and improve outcomes of patients suffering from concussion.
Evaluating Quantitative Pupillometry in Athletes as a Biomarker of Mild Traumatic Brain Injury
This proposal aims to carefully evaluate Quantitative pupillometry (QP) as a potential diagnostic tool to identify brain dysfunction associated with mTBI. Quantitative pupillometry (QP) is the precise measurement of eye pupil characteristics using a dedicated device known as a pupillometer. A pupillometer delivers a light stimulus to the eye and tracks how pupil size changes in response. The results of this study will provide substantial normative data, will identify differences in QP between acutely concussed athletes and control athletes, and will correlate high-acceleration hits with QP.
Orthostatic Heart Rate after Sport Related Concussion
The objective of this study is to determine if there is an orthostatic vitals signature that is unique to acute concussion that would help with the diagnosis of concussion. Our working hypothesis is that the CNS metabolic changes after concussion alter the autonomic control of heart rate in patients with acute concussion. This change in regulation can be detected as a positive finding on standard orthostatic testing after concussion.
Evaluation of Recovery from Sport Related Concussion
The aim of this study is to quantify success in safely returning athletes to sport following evaluation in the NeuroSport outpatient clinic and completion of a graded return to play process. The aim will be accomplished by retrospectively identifying patients who were cleared for sport participation in the NeuroSport clinic and accessing the frequency at which they were able to return to sport without return of symptoms within 2 weeks of completing the return to play to progression. Return to sport without symptoms within two weeks will be determined by self/parent report by phone survey.
Neurologic improvement with guided physical therapy return to play activities for concussion
The objective of this study is to determine if guided sub-symptomatic threshold physical exertion hastens recovery from sports-related concussion. This is a retrospective chart review of SRC patients from September 2016 through January 2017. Patients who underwent controlled physical exertion while symptomatic within 15 days of their concussion were included in the intervention group. Those who did not undergo this testing, were asymptomatic at time of testing, or who underwent testing after 15 days from their concussion were included in the non-intervention group.
Clinical Features of Chronic Traumatic Encephalopathy
The purpose of the study is to gather clinical data from patients with concerns of suffering from long-term consequences of repetitive head trauma. The preponderance of studies indicates that a small number of concussions with normal recovery does not result in neuropsychiatric or cognitive problems later in life. Epidemiologic studies from the Mayo Clinic did not identify any long-term neurologic problems in those who participated in contact sports, i.e. football and wrestling compared to those who did not participate in these sports. Although there has been substantial media coverage of potential long-term neurologic consequences of participation in American professional football, the incidence of neurologic diseases is uncertain. It is clear, primarily from studies of retired boxers, that some individuals appear to have developed neurologic problems secondary to repetitive mild head trauma in their boxing carriers. Researchers have discovered microscopic brain changes in individuals exposed to repetitive mild head trauma, chronic traumatic encephalopathy (CTE). A diagnosis of CTE is made by looking at brain tissue under a microscope. At this point we do not know what consequences these microscopic changes have during the lives of those diagnosed after death with CTE. While ongoing research efforts attempt to further clarify the association of head trauma exposure, clinical symptoms, and neuropathological changes, we have developed a clinical approach to the spectrum of symptoms thought to be caused by a history of repetitive mild head trauma, traumatic encephalopathy syndrome. This approach can be applied to the evaluation and diagnosis while the patient is still alive.
Baseline Concussion Symptom Score Differences Between Gender, Sport or Level of Play
The objective of this study is to determine if baseline concussion symptoms scores in athletes prior to the start of their season vary by gender, sport, or level of play. Concussion is a clinical diagnosis that includes an appropriate clinical scenario, reporting of symptoms through a post-concussion symptom score list, and an objective neurologic exam. Symptom reporting is considered when determining if an athlete has recovered from their concussion. Recent studies have shown that athletes at baseline can report symptoms at a rate high enough to meet criteria for post-concussion syndrome without any history of concussion. A goal of this study is to determine factors that lead to differences among symptom reporting in distinct athlete populations to aid in clinical decision making.
In Fall 2018 Dr. Lorincz was part of the leadership team that successfully applied for a University of Michigan Biosciences Initiative grant. The $5.6-million-dollar grant will support creation of the Michigan Concussion Center, a Category 1 University of Michigan Center. The Michigan NeuroSport Research program is an integral part of the Michigan Concussion Center. Dr. Lorincz is a founding member of the Michigan Concussion Center, a member of the executive committee; a four-person group the will lead the Michigan Concussion Center, and serves as the co-director the Michigan Concussion Center Clinical Core. It is anticipated that the Michigan Concussion Center will provide the critical infrastructure and foster collaborations to accelerate and advance future clinical and translational concussion research. A goal of the Michigan Concussion Center is to position the University of Michigan as a leader in concussion research and a coordinating center for pivotal trials that will positively transform the concussion care landscape.
This research has led to the following publications:
- Reams N, Eckner J, Almeida A, Aagesen A, Giordani B, Paulson H, Lorincz M, Kutcher J. A clinical approach to the diagnosis of traumatic encephalopathy syndrome: A Review. JAMA Neurol 73(6): 743-9, 2016.
- Swallow J, Joseph J, Willsey K, Almeida A, Lorincz M, Park P, Szerlip N, Broglio S: Online postconcussion return-to-play instructions. Journal of Neurosurgery: Pediatrics 21(1):44-48, 2018. PM29125444
- Alsalaheen B, Bean R, Almeida A, Eckner J, Lorincz M: Characterization of cervical neuromuscular response to head-neck perturbation in active young adults. J Electromyogr Kinesiol 39: 70-76, 2018. PM29413455
- Almeida AA, Lorincz MT, Hashikawa AN: Recent Advances in Pediatric Concussion and Mild Traumatic Brain Injury. Pediatr Clin North Am 65(6): 1151-1166, 2018. PM30446054
- Alsalaheen B, Bean R, Almeida A, Eckner J, Lorincz M: Characterization of cervical neuromuscularresponse to head-neck perturbation in active young adults. J Electromyogr Kinesiol 39: 70-76, 2018. PM29413455
- Popovich M, Almeida A, Freeman J, Eckner J, Alsalaheen B, Lorincz M, Sas A: Use of Supervised. Exercise During Recovery Following Sports-Related Concussion Clinical Journal of Sport Medicine. (In Press)
- Alsalaheen B, McCloskey K, Bean R, Almeida A, Eckner J, Lorincz M: Women and men use different strategies to stabilize the head in response to impulsive loading: implications for concussion injury risk. Journal of Orthopaedic & Sports Physical Therapy. (In Press)
Wilson’s Disease Related Research
The focus of my research in Wilson’s disease has been to understand the neurologic manifestations of Wilson’s disease and to develop safe and effective treatments for Wilson’s disease. Wilson’s disease is a neurodegenerative copper metabolism disease that is fatal if unrecognized and untreated. I have been involved in clinical trials of treatment in Wilson’s disease beginning in 1999.
This research has led to the following publications:
- Brewer GJ, Askari F, Lorincz MT, Carlson M, Schilsky M, Kluin KJ, Hedera P, Moretti P, Fink JK, Tankanow R, Dick RB, Sitterly J: Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease. Arch. Neurol. 63(4): 521-7, 2006. PM16606763
- Brewer GJ, Askari F, Dick RB, Sitterly J, Fink JK, Carlson M, Kluin KJ, Lorincz MT: Treatment of Wilson's disease with tetrathiomolybdate: V. control of free copper by tetrathiomolybdate and a comparison with trientine. Transl Res 154(2): 70-7, 2009. PM19595438/PMC-
- Lorincz MT: Neurologic Wilson's disease. Ann. N. Y. Acad. Sci. 1184: 173-87, 2010. PM20146697
- Burke JF, Dayalu P, Nan B, Askari F, Brewer GJ, Lorincz MT: Prognostic significance of neurologic examination findings in Wilson disease. Parkinsonism Relat. Disord. 17(7): 551-6, 2011. PM21641265
- Lorincz MT: Recognition and treatment of neurologic Wilson's disease Semin Neurol 32(5): 538-543, 2012. PM23677665
- Lorincz MT: Neurologic Wilson's Disease. MedLink Neurology, Gilman S, editor MedLink Corporation:San Diego, Available at www.medlink.com. Annually updated 2008-2018, 2008.
- Brewer GJ, Askari F, Lorincz MT, Carlson MD, Schilsky M, Kluin KJ, Hedera P, Moretti P, Fink JK,Tankanow R, Dick RB, Sitterly J: Tetrathiolmolybdate versus Trientine in the Initial Treatment of Wilson's Disease. Progress in Neurotherapeutics and Neuropsychopharmacology, Cummings, JL Editor-in-Chief Cambridge University Press, Cambridge, UK, 2008. 153-166
- Lorincz M: Wilson’s Disease and Related Copper Disorders. Handbook of Clinical Neurology, Aminoff, Boller, Swaab Elsevier, 2018, 18, 279-292.
I am currently a Co-investigator with effort on a phase III trial for Wilson’s disease. A Phase 3, Randomized, Rater-Blinded, Multi-Centre Study to Evaluate the Efficacy and Safety of WTX101 Administered for 48 Weeks Versus Standard of Care in Wilson Disease Subjects Aged 18 and Older with an Extension Phase of up to 60 Months (Wilson Therapeutics)