Michael J. Ellis

Physiological, vestibulo-ocular and cervicogenic post-concussion disorders: An evidence-based classification system with directions for treatment

Abstract Primary objective: To present a novel pathophysiological approach to acute concussion and post-concussion syndrome (PCS). Research design: Review of the literature Methods and procedures: PubMed searches were performed to identify articles related to the pathophysiology and treatment of concussion and PCS. Relevant articles that contributed to the primary objective of the paper were included. Main outcome and results: This paper presents an evidence-based approach to acute concussion and PCS that focuses on the identification of specific post-concussion disorders (PCDs) caused by impairments in global brain metabolism (Physiologic PCD) or neurological sub-system dysfunction (Vestibulo-ocular PCD and Cervicogenic PCD) that can be distinguished by features of the clinical history, physical examination and treadmill exercise testing. This novel approach also allows for the initiation of evidence-based, multi-disciplinary therapeutic interventions that can improve individual symptoms and promote efficient neurological recovery. Conclusion: Future studies incorporating neuro-imaging and exercise science techniques are underway at the author’s institutions to validate this novel pathophysiological approach to acute concussion and PCS.

Psychiatric outcomes after pediatric sports-related concussion

OBJECT The objectives of this study were twofold: (1) to examine the prevalence of emotional symptoms among children and adolescents with a sports-related concussion (SRC) who were referred to a multidisciplinary pediatric concussion program and (2) to examine the prevalence, clinical features, risk factors, and management of postinjury psychiatric outcomes among those in this clinical population. METHODS The authors conducted a retrospective chart review of all patients with SRC referred to a multidisciplinary pediatric concussion program between September 2013 and October 2014. Clinical assessments carried out by a single neurosurgeon included clinical history, physical examination, and Post-Concussion Symptom Scale (PCSS) scoring. Postinjury psychiatric outcomes were defined as a subjective worsening of symptoms of a preinjury psychiatric disorder or new and isolated suicidal ideation or diagnosis of a novel psychiatric disorder (NPD). An NPD was defined as a newly diagnosed psychiatric disorder that occurred in a patient with or without a lifetime preinjury psychiatric disorder after a concussion. Clinical resources, therapeutic interventions, and clinical and return-to-play outcomes are summarized. RESULTS One hundred seventy-four patients (mean age 14.2 years, 61.5% male) were included in the study. At least 1 emotional symptom was reported in 49.4% of the patients, and the median emotional PCSS subscore was 4 (interquartile range 1-8) among those who reported at least 1 emotional symptom. Overall, 20 (11.5%) of the patients met the study criteria for a postinjury psychiatric outcome, including 14 patients with an NPD, 2 patients with isolated suicidal ideation, and 4 patients with worsening symptoms of a preinjury psychiatric disorder. Female sex, a higher initial PCSS score, a higher emotional PCSS subscore, presence of a preinjury psychiatric history, and presence of a family history of psychiatric illness were significantly associated with postinjury psychiatric outcomes. Interventions for patients with postinjury psychiatric outcomes included pharmacological therapy alone in 2 patients (10%), cognitive behavioral therapy alone in 4 (20%), multimodal therapy in 9 (45%), and no treatment in 5 (25%). Overall, 5 (25%) of the patients with postinjury psychiatric disorders were medically cleared to return to full sports participation, whereas 5 (25%) were lost to follow-up and 9 (45%) remained in treatment by the multidisciplinary concussion program at the end of the study period. One patient who was asymptomatic at the time of initial consultation committed suicide. CONCLUSIONS Emotional symptoms were commonly reported among pediatric patients with SRC referred to a multidisciplinary pediatric concussion program. In some cases, these symptoms contributed to the development of an NPD, isolated suicidal ideation, and worsening symptoms of a preexisting psychiatric disorder. Future research is needed to clarify the prevalence, pathophysiology, risk factors, and evidence-based management of postinjury psychiatric outcomes after pediatric SRC. Successful management of these patients requires prompt recognition and multidisciplinary care by experts with clinical training and experience in concussion and psychiatry.

Vestibulo-ocular dysfunction in pediatric sports-related concussion

OBJECT The objective of this study was 2-fold: 1) to examine the prevalence of vestibulo-ocular dysfunction (VOD) among children and adolescents with acute sports-related concussion (SRC) and postconcussion syndrome (PCS) who were referred to a multidisciplinary pediatric concussion program; and 2) to determine if VOD is associated with the development of PCS in this cohort. METHODS The authors conducted a retrospective review of all patients with acute SRC (presenting 30 days or less postinjury) and PCS (3 or more symptoms for at least 1 month) referred to a multidisciplinary pediatric concussion program between September 2013 and July 2014. Initial assessment included clinical history, physical examination, and Post-Concussion Symptom Scale assessment. Patients were also assessed for VOD, which was defined as more than one subjective vestibular and oculomotor complaint (dizziness, blurred vision, and so on) and more than one objective physical examination finding (abnormal smooth pursuits, saccades, vestibulo-ocular reflex, and so on). This study was approved by the local institutional ethics review board. RESULTS A total of 101 patients (mean age 14.2 years, SD 2.3 years; 63 male and 38 female patients) participated, including 77 (76.2%) with acute SRC and 24 (23.8%) with PCS. Twenty-two of the 77 patients (28.6%) with acute SRC and 15 of the 24 (62.5%) with PCS met the clinical criteria for VOD. The median duration of symptoms was 40 days (interquartile range [IQR] 28.5-54 days) for patients with acute SRC who had VOD compared with 21 days (IQR 13-32 days) for those without VOD (p = 0.0001). There was a statistically significant increase in the adjusted odds of developing PCS among patients with acute SRC who had VOD compared with those without VOD (adjusted OR 4.10; 95% CI 1.04-16.16). CONCLUSIONS Evidence of VOD was detected in a significant proportion of children and adolescents with acute SRC and PCS who were referred to a multidisciplinary pediatric concussion program. This clinical feature was a significant risk factor for the subsequent development of PCS in this pediatric acute SRC cohort.

Neuroimaging findings in pediatric sports-related concussion.

OBJECT The goal in this review was to summarize the results of clinical neuroimaging studies performed in patients with sports-related concussion (SRC) who were referred to a multidisciplinar ypediatric concussion program. METHODS The authors conducted a retrospective review of medical records and neuroimaging findings for all patients referred to a multidisciplinary pediatric concussion program between September 2013 and July 2014. Inclusion criteria were as follows: 1) age ≤ 19 years; and 2) physician-diagnosed SRC. All patients underwent evaluation and follow-up by the same neurosurgeon. The 2 outcomes examined in this review were the frequency of neuroimaging studies performed in this population (including CT and MRI) and the findings of those studies. Clinical indications for neuroimaging and the impact of neuroimaging findings on clinical decision making were summarized where available. This investigation was approved by the local institutional ethics review board. RESULTS A total of 151 patients (mean age 14 years, 59% female) were included this study. Overall, 36 patients (24%) underwent neuroimaging studies, the results of which were normal in 78% of cases. Sixteen percent of patients underwent CT imaging; results were normal in 79% of cases. Abnormal CT findings included the following: arachnoid cyst (1 patient), skull fracture (2 patients), suspected intracranial hemorrhage (1 patient), and suspected hemorrhage into an arachnoid cyst (1 patient). Eleven percent of patients underwent MRI; results were normal in 75% of cases. Abnormal MRI findings included the following: intraparenchymal hemorrhage and sylvian fissure arachnoid cyst (1 patient); nonhemorrhagic contusion (1 patient); demyelinating disease (1 patient); and posterior fossa arachnoid cyst, cerebellar volume loss, and nonspecific white matter changes (1 patient). CONCLUSIONS Results of clinical neuroimaging studies are normal in the majority of pediatric patients with SRC. However, in selected cases neuroimaging can provide information that impacts decision making about return to play and retirement from the sport.

Brain MRI CO2 Stress Testing: A Pilot Study in Patients with Concussion

Background There is a real need for quantifiable neuro-imaging biomarkers in concussion. Here we outline a brain BOLD-MRI CO2 stress test to assess the condition. Methods This study was approved by the REB at the University of Manitoba. A group of volunteers without prior concussion were compared to post-concussion syndrome (PCS) patients – both symptomatic and recovered asymptomatic. Five 3-minute periods of BOLD imaging at 3.0 T were studied – baseline 1 (BL1– at basal CO2 tension), hypocapnia (CO2 decreased ∼5 mmHg), BL2, hypercapnia (CO2 increased ∼10 mmHg) and BL3. Data were processed using statistical parametric mapping (SPM) for 1st level analysis to compare each subject’s response to the CO2 stress at the p = 0.001 level. A 2nd level analysis compared each PCS patient’s response to the mean response of the control subjects at the p = 0.05 level. Results We report on 5 control subjects, 8 symptomatic and 4 asymptomatic PCS patients. Both increased and decreased response to CO2 was seen in all PCS patients in the 2nd level analysis. The responses were quantified as reactive voxel counts: whole brain voxel counts (2.0±1.6%, p = 0.012 for symptomatic patients for CO2 response < controls and 3.0±5.1%, p = 0.139 for CO2 response > controls: 0.49±0.31%, p = 0.053 for asymptomatic patients for CO2 response < controls and 4.4±6.8%, p = 0.281 for CO2 response > controls). Conclusions Quantifiable alterations in regional cerebrovascular responsiveness are present in concussion patients during provocative CO2 challenge and BOLD MRI and not in healthy controls. Future longitudinal studies must aim to clarify the relationship between CO2 responsiveness and individual patient symptoms and outcomes.

Brain magnetic resonance imaging CO2 stress testing in adolescent postconcussion syndrome

OBJECT A neuroimaging assessment tool to visualize global and regional impairments in cerebral blood flow (CBF) and cerebrovascular responsiveness in individual patients with concussion remains elusive. Here the authors summarize the safety, feasibility, and results of brain CO2 stress testing in adolescents with postconcussion syndrome (PCS) and healthy controls. METHODS This study was approved by the Biomedical Research Ethics Board at the University of Manitoba. Fifteen adolescents with PCS and 17 healthy control subjects underwent anatomical MRI, pseudo-continuous arterial spin labeling MRI, and brain stress testing using controlled CO2 challenge and blood oxygen level-dependent (BOLD) MRI. Post hoc processing was performed using statistical parametric mapping to determine voxel-by-voxel regional resting CBF and cerebrovascular responsiveness of the brain to the CO2 stimulus (increase in BOLD signal) or the inverse (decrease in BOLD signal). Receiver operating characteristic (ROC) curves were generated to compare voxel counts categorized by control (0) or PCS (1). RESULTS Studies were well tolerated without any serious adverse events. Anatomical MRI was normal in all study participants. No differences in CO2 stimuli were seen between the 2 participant groups. No group differences in global mean CBF were detected between PCS patients and healthy controls. Patient-specific differences in mean regional CBF and CO2 BOLD responsiveness were observed in all PCS patients. The ROC curve analysis for brain regions manifesting a voxel response greater than and less than the control atlas (that is, abnormal voxel counts) produced an area under the curve of 0.87 (p < 0.0001) and 0.80 (p = 0.0003), respectively, consistent with a clinically useful predictive model. CONCLUSIONS Adolescent PCS is associated with patient-specific abnormalities in regional mean CBF and BOLD cerebrovascular responsiveness that occur in the setting of normal global resting CBF. Future prospective studies are warranted to examine the utility of brain MRI CO2 stress testing in the longitudinal assessment of acute sports-related concussion and PCS.

Neuroimaging Assessment of Cerebrovascular Reactivity in Concussion: Current Concepts, Methodological Considerations, and Review of the Literature

Concussion is a form of traumatic brain injury (TBI) that presents with a wide spectrum of subjective symptoms and few objective clinical findings. Emerging research suggests that one of the processes that may contribute to concussion pathophysiology is dysregulation of cerebral blood flow (CBF) leading to a mismatch between CBF delivery and the metabolic needs of the injured brain. Cerebrovascular reactivity (CVR) is defined as the change in CBF in response to a measured vasoactive stimulus. Several magnetic resonance imaging (MRI) techniques can be used as a surrogate measure of CBF in clinical and laboratory studies. In order to provide an accurate assessment of CVR, these sequences must be combined with a reliable, reproducible vasoactive stimulus that can manipulate CBF. Although CVR imaging currently plays a crucial role in the diagnosis and management of many cerebrovascular diseases, only recently have studies begun to apply this assessment tool in patients with concussion. In order to evaluate the quality, reliability, and relevance of CVR studies in concussion, it is important that clinicians and researchers have a strong foundational understanding of the role of CBF regulation in health, concussion, and more severe forms of TBI, and an awareness of the advantages and limitations of currently available CVR measurement techniques. Accordingly, in this review, we (1) discuss the role of CVR in TBI and concussion, (2) examine methodological considerations for MRI-based measurement of CVR, and (3) provide an overview of published CVR studies in concussion patients.

Multi-Disciplinary Management of Athletes with Post-Concussion Syndrome: An Evolving Pathophysiological Approach

Historically, patients with sports-related concussion (SRC) have been managed in a uniform fashion consisting mostly of prescribed physical and cognitive rest with the expectation that all symptoms will spontaneously resolve with time. Although this approach will result in successful return to school and sports activities in the majority of athletes, an important proportion will develop persistent concussion symptoms characteristic of post-concussion syndrome (PCS). Recent advances in exercise science, neuroimaging, and clinical research suggest that the clinical manifestations of PCS are mediated by unique pathophysiological processes that can be identified by features of the clinical history and physical examination as well as the use of graded aerobic treadmill testing. Athletes who develop PCS represent a unique population whose care must be individualized and must incorporate a rehabilitative strategy that promotes enhanced recovery of concussion-related symptoms while preventing physical deconditioning. In this review, we present our evolving evidence-based approach to evaluation and management of athletes with PCS that aims to identify the pathophysiological mechanisms mediating persistent concussion symptoms and guides the initiation of individually tailored rehabilitation programs that target these processes. In addition, we outline the important qualified roles that multi-disciplinary healthcare professionals can play in the management of this patient population, and discuss where future research efforts must be focused to further evaluate this evolving pathophysiological approach.

Clinical predictors of vestibulo-ocular dysfunction in pediatric sports-related concussion

OBJECTIVE There were 2 objectives of this study. The first objective was to identify clinical variables associated with vestibulo-ocular dysfunction (VOD) detected at initial consultation among pediatric patients with acute sports-related concussion (SRC) and postconcussion syndrome (PCS). The second objective was to reexamine the prevalence of VOD in this clinical cohort and evaluate the effect of VOD on length of recovery and the development of PCS. METHODS A retrospective review was conducted for all patients with acute SRC and PCS who were evaluated at a pediatric multidisciplinary concussion program from September 2013 to May 2015. Acute SRS was defined as presenting < 30 days postinjury, and PCS was defined according to the International Classification of Diseases, 10th Revision criteria and included being symptomatic 30 days or longer postinjury. The initial assessment included clinical history and physical examination performed by 1 neurosurgeon. Patients were assessed for VOD, defined as the presence of more than 1 subjective vestibular and oculomotor complaint (dizziness, diplopia, blurred vision, etc.) and more than 1 objective physical examination finding (abnormal near point of convergence, smooth pursuits, saccades, or vestibulo-ocular reflex testing). Poisson regression analysis was used to identify factors that increased the risk of VOD at initial presentation and the development of PCS. RESULTS Three hundred ninety-nine children, including 306 patients with acute SRC and 93 with PCS, were included. Of these patients, 30.1% of those with acute SRC (65.0% male, mean age 13.9 years) and 43.0% of those with PCS (41.9% male, mean age 15.4 years) met the criteria for VOD at initial consultation. Independent predictors of VOD at initial consultation included female sex, preinjury history of depression, posttraumatic amnesia, and presence of dizziness, blurred vision, or difficulty focusing at the time of injury. Independent predictors of PCS among patients with acute SRC included the presence of VOD at initial consultation, preinjury history of depression, and posttraumatic amnesia at the time of injury. CONCLUSIONS This study identified important potential risk factors for the development of VOD following pediatric SRC. These results provide confirmatory evidence that VOD at initial consultation is associated with prolonged recovery and is an independent predictor for the development of PCS. Future studies examining clinical prediction rules in pediatric concussion should include VOD. Additional research is needed to elucidate the natural history of VOD following SRC and establish evidence-based indications for targeted vestibular rehabilitation.

Graded aerobic treadmill testing in pediatric sports-related concussion: safety, clinical use, and patient outcomes

OBJECTIVE The objectives of this study were 2-fold: 1) to evaluate the safety, tolerability, and clinical use of graded aerobic treadmill testing in pediatric patients with sports-related concussion (SRC), and 2) to evaluate the clinical outcomes of treatment with a submaximal aerobic exercise program in patients with physiological post-concussion disorder (PCD). METHODS The authors conducted a retrospective chart review of pediatric patients (age < 20 years) with SRC who were referred to a multidisciplinary pediatric concussion program and underwent graded aerobic treadmill testing between October 9, 2014, and February 11, 2016. Clinical assessments were carried out by a single neurosurgeon and included clinical history taking, physical examination, and recording specific patient-reported concussion-related symptoms using the Post-Concussion Symptom Scale (PCSS). Graded aerobic treadmill testing using a modified Balke protocol for incremental increases in intensity was used as a diagnostic tool to assess physiological recovery, classify post-concussion syndrome (PCS) subtype, and reassess patients following treatment. Patients with a symptom-limited threshold on treadmill testing (physiological PCD) were treated with an individually tailored submaximal exercise prescription and multidisciplinary targeted therapies. RESULTS One hundred six patients (mean age 15.1 years, range 11-19 years) with SRC underwent a total of 141 treadmill tests. There were no serious complications related to treadmill testing in this study. Overall, 138 (97.9%) of 141 tests were well tolerated and contributed valuable clinical information. Treadmill testing confirmed physiological recovery in 63 (96.9%) of 65 patients tested, allowing successful return to play in 61 (93.8%). Treadmill testing was used to diagnose physiological PCD in 58 patients and cervicogenic PCD in 1 patient. Of the 41 patients with physiological PCD who had complete follow-up and were treated with tailored submaximal exercise prescription, 37 (90.2%) were classified as clinically improved and 33 (80.5%) successfully returned to sporting activities. Patients who did not respond or experienced an incomplete response to submaximal aerobic exercise treatment included 7 patients with migraine headaches and 1 patient with a postinjury psychiatric disorder. CONCLUSIONS Graded aerobic treadmill testing is a safe, tolerable, and clinically valuable tool that can assist in the evaluation and management of pediatric SRC. Future research is needed to confirm the clinical value of this tool in return-to-play decision making. Studies are also needed to understand the pathophysiology of physiological PCD and the effects of targeted treatment.