Rebekah Mannix

Time Interval Between Concussions and Symptom Duration

OBJECTIVE: To test the hypothesis that children with a previous history of concussion have a longer duration of symptoms after a repeat concussion than those without such a history. METHODS: Prospective cohort study of consecutive patients 11 to 22 years old presenting to the emergency department of a childrens hospital with an acute concussion. The main outcome measure was time to symptom resolution, assessed by the Rivermead Post-Concussion Symptoms Questionnaire (RPSQ). Patients and providers completed a questionnaire describing mechanism of injury, associated symptoms, past medical history, examination findings, diagnostic studies, and the RPSQ. Patients were then serially administered the RPSQ for 3 months after the concussion or until all symptoms resolved. RESULTS: A total of 280 patients were enrolled over 12 months. Patients with a history of previous concussion had a longer duration of symptoms than those without previous concussion (24 vs 12 days, P = .02). Median symptom duration was even longer for patients with multiple previous concussions (28 days, P = .03) and for those who had sustained a concussion within the previous year (35 days, P = .007) compared with patients without those risk factors. In a multivariate model, previous concussion, absence of loss of consciousness, age ≥13, and initial RPSQ score >18 were significant predictors of prolonged recovery. CONCLUSIONS: Children with a history of a previous concussion, particularly recent or multiple concussions, are at increased risk for prolonged symptoms after concussion. These findings have direct implications on the management of patients with concussion who are at high risk for repeat injuries.

Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy

Traumatic brain injury (TBI), characterized by acute neurological dysfunction, is one of the best known environmental risk factors for chronic traumatic encephalopathy and Alzheimer’s disease, the defining pathologic features of which include tauopathy made of phosphorylated tau protein (P-tau). However, tauopathy has not been detected in the early stages after TBI, and how TBI leads to tauopathy is unknown. Here we find robust cis P-tau pathology after TBI in humans and mice. After TBI in mice and stress in vitro, neurons acutely produce cis P-tau, which disrupts axonal microtubule networks and mitochondrial transport, spreads to other neurons, and leads to apoptosis. This process, which we term ‘cistauosis’, appears long before other tauopathy. Treating TBI mice with cis antibody blocks cistauosis, prevents tauopathy development and spread, and restores many TBI-related structural and functional sequelae. Thus, cis P-tau is a major early driver of disease after TBI and leads to tauopathy in chronic traumatic encephalopathy and Alzheimer’s disease. The cis antibody may be further developed to detect and treat TBI, and prevent progressive neurodegeneration after injury.Traumatic brain injury (TBI), characterized by acute neurological dysfunction, is one of the best known environmental risk factors for chronic traumatic encephalopathy (CTE) and Alzheimers disease (AD), whose defining pathologic features include tauopathy made of phosphorylated tau (p-tau). However, tauopathy has not been detected in early stages after TBI and how TBI leads to tauopathy is unknown. Here we find robust cis p-tau pathology after sport- and military-related TBI in humans and mice. Acutely after TBI in mice and stress in vitro, neurons prominently produce cis p-tau, which disrupts axonal microtubule network and mitochondrial transport, spreads to other neurons, and leads to apoptosis. This process, termed “cistauosis”, appears long before other tauopathy. Treating TBI mice with cis antibody blocks cistauosis, prevents tauopathy development and spread, and restores many TBI-related structural and functional sequelae. Thus, cis p-tau is a major early driver after TBI and leads to tauopathy in CTE and AD, and cis antibody may be further developed to detect and treat TBI, and prevent progressive neurodegeneration after injury.

Effect of Cognitive Activity Level on Duration of Post-Concussion Symptoms

OBJECTIVE: To determine the effect of cognitive activity level on duration of post-concussion symptoms. METHODS: We conducted a prospective cohort study of patients who presented to a Sports Concussion Clinic within 3 weeks of injury between October 2009 and July 2011. At each visit, patients completed a scale that recorded their average level of cognitive activity since the previous visit. The product of cognitive activity level and days between visits (cognitive activity-days) was calculated and divided into quartiles. Kaplan-Meier Product Limit method was used to generate curves of symptom duration based on cognitive activity level. To adjust for other possible predictors of concussion recovery, we constructed a Cox proportional hazard model with cognitive activity-days as the main predictor. RESULTS: Of the 335 patients included in the study, 62% were male, 19% reported a loss of consciousness, and 37% reported experiencing amnesia at the time of injury. The mean age of participants was 15 years (range, 8–23) and the mean number of previous concussions was 0.76; 39% of athletes had sustained a previous concussion. The mean Post-Concussion Symptom Scale score at the initial visit was 30 (SD, 26). The overall mean duration of symptoms was 43 days (SD, 53). Of all variables assessed, only total symptom burden at initial visit and cognitive activity level were independently associated with duration of symptoms. CONCLUSIONS: Increased cognitive activity is associated with longer recovery from concussion. This study supports the use of cognitive rest and adds to the current consensus opinion.

Pediatric concussions in United States emergency departments in the years 2002 to 2006.

OBJECTIVES To estimate the incidence and demographics of concussions in children coming to emergency departments (EDs) in the United States and describe the rates of neuroimaging and follow-up instructions in these patients. STUDY DESIGN This is a cross-sectional study of children 0 to 19 years old diagnosed with concussion from the National Hospital Ambulatory Medical Care Survey. National Hospital Ambulatory Medical Care Survey collects data on approximately 25,000 visits annually to 600 randomly selected hospital emergency and outpatient departments. We examined visits to United States emergency departments between 2002 and 2006. Simple descriptive statistics were used. RESULTS Of the 50,835 pediatric visits in the 5-year sample, 230 observations, representing 144,000 visits annually, were for concussions. Sixty-nine percent of concussion visits were by males. Thirty percent were sports-related. Sixty-nine percent of patients diagnosed with a concussion had head imaging. Twenty-eight percent of patients were discharged without specific instructions to follow-up with an outpatient provider for further treatment. CONCLUSIONS Approximately 144,000 pediatric patients present to emergency departments each year with a concussion. Most of these patients undergo computed tomography of the head, and nearly one-third are discharged without specific instructions to follow-up with an outpatient provider for further treatment.

Acute Pediatric Rhabdomyolysis: Causes and Rates of Renal Failure

OBJECTIVES. The goals were to (1) compare the causes, clinical presentation, and prevalence of acute renal failure in pediatric rhabdomyolysis with the published data for adults; (2) determine predictors of acute renal failure in pediatric patients with rhabdomyolysis; and (3) explore the relationship of acute renal failure with treatment modalities such as fluid and bicarbonate administration. METHODS. We performed a retrospective chart review to identify patients with creatinine kinase levels of >1000 IU/L who were treated in the emergency department of a tertiary pediatric hospital between 1993 and 2003, and we constructed regression models. RESULTS. Two hundred ten patients were studied. One hundred ninety-one patients met study eligibility (128 male and 63 female), with a median age of 11 years. The most common documented symptoms were muscle pain (45%), fever (40%), and symptoms of viral infection (39%). The most common causes of pediatric rhabdomyolysis were viral myositis (38%), trauma (26%), and connective tissue disease (5%). Six of 37 patients with creatinine kinase levels of ≥6000 IU/L had previously undiagnosed dermatomyositis or hereditary metabolic disease, compared with 10 of 154 patients with creatinine kinase levels of 1000 to 5999 IU/L. Nine of 191 patients developed acute renal failure. None of 99 patients with initial urinary heme dipstick results of <2+ developed acute renal failure, compared with 9 of 44 patients with urinary heme dipstick results of ≥2+. Higher initial creatinine kinase levels and higher fluid administration rates were associated with higher maximal creatinine levels. CONCLUSIONS. The cause of acute pediatric rhabdomyolysis is different from that of adult rhabdomyolysis. The risk of acute renal failure in children is much less than the risk reported for adults.

Symptom Severity Predicts Prolonged Recovery after Sport-Related Concussion, but Age and Amnesia Do Not

OBJECTIVE To identify predictors of prolonged symptoms in athletes who sustain concussions. STUDY DESIGN This was a multicenter prospective cohort study of patients in 2 sport concussion clinics. Possible predictors of prolonged symptoms from concussion were compared in 2 groups, those whose symptoms resolved within 28 days and those whose symptoms persisted beyond 28 days. Candidate predictor variables were entered into a logistic regression model that was used to generate aORs. RESULTS A total of 182 patients met the inclusion criteria during the study period. The mean patient age was 15.2 ± 3.04 years. More than one-third of the patients (n = 65) underwent computerized neurocognitive testing on their initial visit. On univariate analyses, Post-Concussion Symptom Scale (PCSS) score and all composite scores on computerized neurocognitive testing were apparently associated with prolonged symptom duration. Sex, age, loss of consciousness at time of injury, and amnesia at time of injury were not associated with prolonged symptom duration. After adjusting for potential confounding, only total PCSS score was associated with the odds of suffering prolonged symptoms. CONCLUSION Further efforts to develop clinical tools for predicting which athletes will suffer prolonged recoveries after concussion should focus on initial symptom score.

Duration and Course of Post-Concussive Symptoms

OBJECTIVES: To examine the incidence, duration, and clinical course of individual post-concussive symptoms in patients presenting to a pediatric emergency department (ED) with a concussion. METHODS: We conducted secondary analysis of a prospective cohort study of patients 11 to 22 years old presenting to the ED of a children’s hospital with an acute concussion. The main outcome measure was duration of symptoms, assessed by the Rivermead Post-Concussion Symptoms Questionnaire (RPSQ). Patients initially completed a questionnaire describing mechanism of injury, associated symptoms, past medical history, and the RPSQ, then were serially administered the RPSQ for 3 months after the concussion or until all symptoms resolved. RESULTS: Headache, fatigue, dizziness, and taking longer to think were the most common symptoms encountered at presentation, whereas sleep disturbance, frustration, forgetfulness, and fatigue were the symptoms most likely to develop during the follow-up period that had not initially been present. Median duration of symptoms was the longest for irritability (16 days), sleep disturbance (16 days), frustration (14 days), and poor concentration (14 days), whereas nausea, depression, dizziness, and double-vision abated most quickly. One month after injury, nearly a quarter of children still complained of headache, >20% suffered from fatigue, and nearly 20% reported taking longer to think. CONCLUSIONS: Among patients presenting to a pediatric ED after a concussion, physical symptoms such as headache predominate immediately after the injury, emotional symptoms tend to develop later in the recovery period, and cognitive symptoms may be present throughout.

Trends in Visits for Traumatic Brain Injury to Emergency Departments in the United States

In the last decade, traumatic brain injury (TBI) garnered increased attention, including public campaigns and legislation to increase awareness and prevent head injuries.1 The Centers for Disease Control and Prevention (CDC) describes TBI as a serious public health concern.2 We sought to describe national trends in emergency department (ED) visits for TBI.

Clinical correlates in an experimental model of repetitive mild brain injury.

Although there is growing awareness of the long‐term cognitive effects of repetitive mild traumatic brain injury (rmTBI; eg, sports concussions), whether repeated concussions cause long‐term cognitive deficits remains controversial. Moreover, whether cognitive deficits depend on increased amyloid β deposition and tau phosphorylation or are worsened by the apolipoprotein E4 allele remains unknown. Here, we use an experimental model of rmTBI to address these clinical controversies.

The prevalence of undiagnosed concussions in athletes.

Objective:Previous studies suggest athletes underreport concussions. We sought to determine whether athletes in our clinics have sustained previous concussions that went undiagnosed. Design:Multicentered cross sectional study. Setting:Two sport concussion clinics. Patients:Patients diagnosed with sport-related concussions or concussions with injury mechanisms and forces similar to those observed in sports were included. Main Outcome Measures:The proportion of patients who answered “yes” to the following question were defined as having a previously undiagnosed concussion: “Have you ever sustained a blow to the head which was NOT diagnosed as a concussion but was followed by one or more of the signs and symptoms listed in the Post Concussion Symptom Scale?” Results:Of the 486 patients included in the final analysis, 148 (30.5%) patients reported a previously undiagnosed concussion. Athletes reporting previously undiagnosed concussions had a higher mean Post Concussion Symptom Scale (PCSS) score (33 vs 25; P < 0.004) and were more likely to have lost consciousness (31% vs 22%; P = 0.038) with their current injury than athletes without previously undiagnosed concussions. Conclusions:Nearly one-third of athletes have sustained previously undiagnosed concussions, defined as a blow to the head followed by the signs and symptoms included in the PCSS. Furthermore, these previously undiagnosed concussions are associated with higher PCSS scores and higher loss of consciousness rates when future concussions occur. Clinical Relevance:Many athletes have sustained previous blows to the head that result in the signs and symptoms of concussion but have not been diagnosed with a concussion. These injuries are associated with increased rates of loss of consciousness and higher symptom scale scores with future concussions.