Hello! Cumulative subconcussive blows are important! The spectrum of disease in chronic traumatic encephalopathy!

J Biomech. 2012 Apr 30;45(7):1265-72. doi: 10.1016/j.jbiomech.2012.01.034. Epub 2012 Feb 28.

Biomechanical correlates of symptomatic and asymptomatic neurophysiological impairment in high schoolfootball.

Breedlove EL, Robinson M, Talavage TM, Morigaki KE, Yoruk U, O'Keefe K, King J, Leverenz LJ, Gilger JW, Nauman EA.

Source

School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907-2088, United States.

Abstract

Concussion is a growing public health issue in the United States, and chronic traumatic encephalopathy (CTE) is the chief long-term concern linked to repeated concussions. Recently, attention has shifted toward subconcussive blows and the role they may play in the development of CTE. We recruited a cohort of high school football players for two seasons of observation. Acceleration sensors were placed in the helmets, and all contact activity was monitored. Pre-season computer-based neuropsychological tests and functional magnetic resonance imaging (fMRI) tests were also obtained in order to assess cognitive and neurophysiological health. In-season follow-up scans were then obtained both from individuals who had sustained a clinically-diagnosed concussion and those who had not. These changes were then related through stepwise regression to history of blows recorded throughout the football season up to the date of the scan. In addition to those subjects who had sustained a concussion, a substantial portion of our cohort who did not sustain concussions showed significant neurophysiological changes. Stepwise regression indicated significant relationships between the number of blows sustained by a subject and the ensuing neurophysiological change. Our findings reinforce the hypothesis that the effects of repetitive blows to the head are cumulative and that repeated exposure to subconcussive blows is connected to pathologically altered neurophysiology.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID:

 

22381736

 

[PubMed - indexed for MEDLINE]

Brain. 2013 Jan;136(Pt 1):43-64. doi: 10.1093/brain/aws307. Epub 2012 Dec 2.

The spectrum of disease in chronic traumatic encephalopathy.

McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC.

Source

United States Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA 02130, USA. ann.mckee@va.gov

Abstract

Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging in age from 17 to 98 years (mean 59.5 years), including 64 athletes, 21 military veterans (86% of whom were also athletes) and one individual who engaged in self-injurious head banging behaviour. Eighteen age- and gender-matched individuals without a history of repetitive mild traumatic brain injury served as control subjects. In chronic traumatic encephalopathy, the spectrum of hyperphosphorylated tau pathology ranged in severity from focal perivascular epicentres of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions, including the medial temporal lobe, thereby allowing a progressive staging of pathology from stages I-IV. Multifocal axonal varicosities and axonal loss were found in deep cortex and subcortical white matter at all stages of chronic traumatic encephalopathy. TAR DNA-binding protein 43 immunoreactive inclusions and neurites were also found in 85% of cases, ranging from focal pathology in stages I-III to widespread inclusions and neurites in stage IV. Symptoms in stage I chronic traumatic encephalopathy included headache and loss of attention and concentration. Additional symptoms in stage II included depression, explosivity and short-term memory loss. In stage III, executive dysfunction and cognitive impairment were found, and in stage IV, dementia, word-finding difficulty and aggression were characteristic. Data on athletic exposure were available for 34 American football players; the stage of chronic traumatic encephalopathy correlated with increased duration offootball play, survival after football and age at death. Chronic traumatic encephalopathy was the sole diagnosis in 43 cases (63%); eight were also diagnosed with motor neuron disease (12%), seven with Alzheimer's disease (11%), 11 with Lewy body disease (16%) and four with frontotemporal lobar degeneration (6%). There is an ordered and predictable progression of hyperphosphorylated tau abnormalities through the nervous system inchronic traumatic encephalopathy that occurs in conjunction with widespread axonal disruption and loss. The frequent association of chronic traumatic encephalopathy with other neurodegenerative disorders suggests that repetitive brain trauma and hyperphosphorylated tau protein deposition promote the accumulation of other abnormally aggregated proteins including TAR DNA-binding protein 43, amyloid beta protein and alpha-synuclein.

PMID:

 

23208308

 

[PubMed - indexed for MEDLINE] 

PMCID:

 

PMC3624697

 [Available on 2014/1/1]

Does second impact syndrome exist?

No one would argue about the rare and often fatal diffuse cerebral swelling following concussion. 

But, many are surprised to learn that there is little evidence to suport a "second impact syndrome". 

It is most likely that there is a genetic susceptibility to brain edema following a concussion.

See the blog by neuropsychologist Dr. Carone below for an excellent summary of the controversy.

JR

"It has often been reported that when a person suffers a second concussion (mild traumatic brain injury) before recovery from the first concussion takes place, that catastrophic brain swelling and death can result. This has been alleged to occur based on anecdotal information and when it happens (usually in young male athletes) it is referred to as “second impact syndrome” (SIS). SIS is often reported as a factual entity in the media and in the medical literature.

However, when one assess the evidence-based data for whether SIS truly exists, we are left with far more questions than answers. As Dr. Paul McCrory and colleagues (2012) put it, “The phenomenon of the second impact syndrome (SIS) continues to appear in the medical literature in spite of the lack of systemic evidence for its existence.” While McCrory's work is accessible through medical libraries, I have never seen in discussed in mainstream media coverage of SIS. Thus, a brief summary is presented below for ease of access for those who are interested....." Full blog article here

Neurology. 1998 Mar;50(3):677-83.

Second impact syndrome.

McCrory PR, Berkovic SF.

Source

Department of Medicine, University of Melbourne, Australia.

Abstract

Diffuse cerebral swelling with delayed catastrophic deterioration, a known complication of brain trauma, has been postulated to occur after repeated concussive brain injury in sports--the "second impact syndrome" (SIS). Certain current concussion management guidelines are contingent upon this assumption. We established criteria for definite, probable, and possible SIS and analyzed all published cases. A total of 17 cases were identified in which the reports described the cases as being consistent with SIS. Of these, only five probable cases of SIS were found based on our diagnostic criteria. We also studied the accuracy of recalled episodes of minor concussion in football players by their teammates because the diagnosis of SIS is usually based on such accounts. We found overreporting of recalled episodes of concussion in teammates when compared with self reports and videotape analysis. Based on case reports, the claim that SIS is a risk factor for diffuse cerebral swelling is not established. Prevention strategies for sports-related cerebral swelling are difficult to implement in the absence of established risk factors.

Curr Sports Med Rep. 2012 Jan-Feb;11(1):21-3. doi: 10.1249/JSR.0b013e3182423bfd.

Second impact syndrome or cerebral swelling after sporting head injury.

McCrory P, Davis G, Makdissi M.

Source

Centre for Health, Exercise and Sports Medicine, The University of Melbourne, Parkville, Victoria, Australia. paulmccr@bigpond.net.au

Abstract

Second impact syndrome is believed to be the catastrophic consequence of repeated head injury in sport. The scientific evidence to support this concept is nonexistent, and belief in the syndrome is based upon the interpretation of anecdotal cases more often than not, lacking sufficient clinical detail to make definitive statements. The fear of this condition has driven many of the current return-to-play guidelines following concussion. Diffuse cerebral swelling (DCS) following a head injury is a well-recognized condition, more common in children than in adults, and usually has a poor outcome.

PMID:

 

22236821

 

[PubMed - indexed for MEDLINE]

Cognitive rest for concussion management lacks data

Cognitive rest for concussion management lacks data

Good debate on concussion treatment data! I suspect that the ER docs and pediatric neurologists are talking about different clinical scenarios. Who would argue with avoiding vigorous athletics or contact injury just after leaving the ER?

But, let's consider a sample of typical school recommendations following a concussion:

Treatment/ Rehabilitation    

"XX ISD athletes who sustain a head injury will be instructed to rest, both 
physically and cognitively.  This means that the athlete will be restricted from athletic 
participation, and should be restricted from recreational exercise, video games/television 
viewing, computer usage, including text messaging"

This can go on for months in some students.

Some schools recommend that students avoid spicy foods. Really?

Where is the pediatric data?

- JR

Cognitive rest for concussion management lacks data

• Infectious Diseases in Children, October 2012
  Joshua Rotenberg, MD; Marc P DiFazio, MD, FAAN; Michael W Kirkwood, PhD

Raising awareness among pediatricians about how to best manage concussions in children and adolescents is important and more information is beginning to appear in various media. However, reports that encourage “cognitive rest” as the cornerstone of concussion treatment are not yet validated.

See Also

• Few pediatricians provide written instructions for cognitive rest ...
• New guidelines established for diagnosis, management of ...
• Cognitive developmental differences nonsignificant for infants ...

Unfortunately, although sports-related concussion is common in childhood, there is a paucity of empirical literature to support rest — cognitive or otherwise — as a management approach. Adding to the confusion, media reports implicate concussion in debilitating neurologic conditions and long-term neurodegenerative conditions; although to date, the evidence here remains speculative based on single case studies or survey data rather than controlled studies.

‘Second-impact syndrome’

There are reasons to briefly interrupt a child’s participation in contact sports after concussion. Patients may be at greater risk for injury, in general, if balance is affected and it allows time for adequate assessment of the injury. However, management during the past decade has emphasized removal from sports participation to lessen the risk for so-called “second-impact syndrome.”

Marc P. DiFazio

This condition reportedly puts the individual at risk for fatal brain edema after a second concussion while still symptomatic from the first. However, critical analysis of the purported syndrome emphasizes the nebulous nature of this condition and even questions its existence. Catastrophic outcomes from sports-related concussion are much more likely to stem from acute intracranial bleeding after single concussions than diffuse edema or back-to-back concussions. Regardless of the exact pathology, death from sports-related head trauma in youth, although tragic in every case, is also several times less likely than death from sports-related cardiovascular events — and even less likely than death from lightning strikes.

Although physical exercise itself has never been implicated in worsening recovery from concussion, complete physical rest is commonly recommended. Additionally, many practitioners now recommend “cognitive rest” to supposedly hasten recovery. Cognitive rest remains ill-defined and usually entails a removal from school and cognitively stressful activities. A return of symptoms (pain, dizziness) upon reintroduction of activity, physical or otherwise, is considered causative of more injury, and further rest is prescribed. Patients are often told to rest until asymptomatic, often resulting in weeks missed from school, sports or extracurricular activities.

Michael W. Kirkwood

Currently, there is no evidence that the brain can be “put to rest” by refraining from such activity, and the increase in symptoms that may be associated with cognitive stress does not imply a worsening of the underlying concussive injury. That is, head pain and other nonspecific symptoms have not been shown to be definitive markers of ongoing cerebral injury. Although cognitive rest certainly sounds logical, brain activity is continuous and is generally uncontrolled by conscious means, and even during sleep intense brain remodeling and activity is evident.

Additionally, there is no good evidence in humans that rest results in brain healing or improved outcomes, and some data actually suggest that activity relatively soon after injury or while symptomatic has no effect on outcomes. Clearly, a standard-of-care guide regarding rest after sports-related concussion does not yet exist.

Negative effects of cognitive rest

Joshua Rotenberg

Some might wonder whether there is really a downside to recommending cognitive rest. The implicit idea in the recommendation for rest is that if this is not followed, problems can be expected. In fact, prospective controlled studies demonstrate that most athletes recover well and relatively quickly with or without rest. More generally, psychoeducation and early reassurance after injury appears to reduce the chance of persistent symptoms after mild traumatic brain injury. This appears to support the clinical impression that patient or parental anxiety after a concussion can exacerbate symptoms and delay a return to typical functioning.

Adolescent obesity leads to midlife morbidity, and correspondingly, middle-aged adults who are obese have increased cardiovascular and neurologic health risks. Additionally, involvement in youth sports has long demonstrated physical and psychological benefits.

Individual approach to assessment

Given the lack of evidence supporting rest or even a symptom-free waiting period subsequent to a concussion, we approach our children and adolescents in a positive and reassuring fashion, avoiding rigid adherence to any particular management strategy. We recommend a return to exercise in a staged fashion, with an allowance for a self-determined escalation in activity, as tolerated. Regarding cognitive stress, we encourage a child’s return to school, albeit with temporary accommodations for headache and any cognitive difficulties that may occur. Frequent breaks and forgiveness for time and work missed are strongly recommended to avoid placing more stress on the student.

Children who experience concussion with recalcitrant symptoms or a previous history of neuropsychiatric difficulties are offered early psychological or medical intervention targeting anxiety, depression, fatigue, sleep difficulties or attentional challenges. Children are seen frequently and are encouraged and reassured that most who experience a mild traumatic brain injury have complete resolution within several weeks. We employ a number of indicators to craft an individual approach to assessment, including physical examination, symptom report, balance assessment, neurocognitive screenings, neuropsychological evaluation and screening for previous neuropsychiatric challenges. This approach is typically welcomed by parents, who are often relieved and reassured by the individualized care.

We hope that professional discourse among pediatric specialists will result in a data-driven approach to management of this common neurologic problem. Allowing anecdotes, popular beliefs or the media to dictate how we address this very frequent and long-standing sports-related complication is imprudent. Recommendations to avoid sports participation or exercise are potentially dangerous — given that more than 20% of children are obese — and as such are at greater risk for neurologic and cardiovascular complications during the lifespan, according to a 2012 study by Dattilo and colleagues.

Pediatricians should encourage exercise and sports participation while offering prudent counseling regarding concussion and brain protection throughout the life span.

• Marc P. DiFazio, MD, FAAN, is the Medical Director of the Regional Outpatient Center and Assistant Professor of Neurology at Children’s National Medical Center in Washington, D.C. He is also Assistant Professor at the Uniformed Services University of the Health Sciences in Bethesda, Md. DiFazio can be reached at: marcdifazio@gmail.com.
  Michael W. Kirkwood, PhD, is from the Department of Physical Medicine & Rehabilitation at University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, Colo. Kirkwood can be reached at: Michael.Kirkwood@childrenscolorado.org.
  Joshua Rotenberg, MD, is Board Certified in Child and Adolescent Neurology and works with the Texas Medical & Sleep Specialists in Houston. Rotenberg can be reached at: pedzzz@gmail.com.
• Disclosure: DiFazio, Kirkwood and Rotenberg report no relevant financial disclosures.

PERSPECTIVE

• We thank Dr. DiFazio and colleagues for their editorial about cognitive rest as a treatment following concussion. Approximately 75% to 80% of traumatic brain injuries are mild and there is robust evidence that these seemingly minor injuries result in poor neurocognitive outcomes in an important proportion of pediatric patients.
  We agree with Dr. DiFazio’s group that there is equivocal evidence supporting, and significant controversy surrounding, ‘second-impact syndrome,’ and that this potential risk of death is extremely rare. However, we do not identify fatality risks due to second-impact syndrome as the driving force behind the recommendation for cognitive and physical rest following concussion. Instead, our focus is on the far more common morbidity and short-term disability following concussion due to metabolic mismatch and associated symptoms in the acute phase immediately following the injury.
  In this early phase, activities that place demands on brain metabolism (ie, physical exercise, learning or recreational activities such as school, video games and texting) divert metabolic resources away from the healing process. Research on pediatric concussion has demonstrated increased energy demand with decreased cerebral blood flow immediately following these injuries. Due to the time course of this physiologic process, treatment in the acute phase differs from management in the chronic stages of concussion. Patients with acute injury are more likely to seek emergency medicine and general pediatric care prior to referral to a subspecialist for more persisting symptoms from concussion. It is during the early initial acute phase post-injury when cognitive rest may be helpful in light of our current understanding of the pathophysiology of concussion.
  While we agree that the evidence surrounding the effectiveness of this treatment is still emerging, there are data supporting cognitive and physical rest immediately following concussion. Animal studies of exercise following traumatic brain injury demonstrate worse outcomes with early exercise, and better outcomes with later exercise. Other research on children with concussion shows increased symptoms and poorer cognitive testing performance with cognitive and physical disability in the early phase following injury, and improved performance with reduced symptoms following cognitive rest.
  Rather than being prescriptive about the absolute duration and of cognitive rest, we emphasize that it is variable, personalized to each specific child and directed by the elicitation of symptoms. We follow a gradual approach to “return to learn” with subsequent “return to play,” whereby patients and their families can continue a self-paced approach to recovery. Patients can progress to the next step in their recovery if symptoms resolve, and revert to a prior step if symptoms are elicited. Our steps, modeled after the Zurich Return to Play guidelines, include a graded re-entry into cognitive activity.
  Rest can vary from a day to a week or more, and is highly individualized. However, after the acute phase a few weeks following injury, cognitive rest has not been demonstrated to be helpful, and may actually be counterproductive. Rather, patients in this stage benefit from active rehabilitation including directed vestibular therapy as well as a graded aerobic therapy program. Of note, as our recommendation for cognitive rest is not synonymous with bed rest, includes a graded return to cognitive activity and is not meant to last indefinitely, we do not think a reasonable period of rest following injury would at all contribute to the emerging obesity epidemic as the authors suggest. Our aim in sports medicine is to return patients back to full participation in sports and other activities as safely and expeditiously as possible given our current understanding of pediatric and adolescent concussion.
  We believe prescribing a combination of appropriate initial rest with a progressive increase in activity in the acute phase, followed by active rehabilitation would in fact minimize the duration of symptomatology, while facilitating a timely return to both cognitive and physical activity.
  We agree with the authors that there is a great amount of needed research on this topic, including identifying the optimal time of rest and risk factors for poor outcomes. We fully support ongoing biomolecular and animal research focused on pathophysiology, biomechanical study of injury mechanisms, epidemiologic analysis of existing patient data, and clinical trials of various treatments in order to further the field of mild traumatic brain injury management. We would encourage that, while further data emerges, recommendations should focus on a “moderate” standpoint, whereby neither strict cognitive and physical rest for a pre-determined time, nor immediate resumption of physical or cognitive activities are recommended following injury. Instead, providers should first ‘do no harm’, and allow, during the acute phase of injury, the brains of acutely concussed children to rest for a reasonable duration that is primarily driven by individual symptomatology, with appropriate rehabilitation for children with chronic, prolonged symptoms.
  Kristy B. Arbogast, PhD
  Matthew F. Grady, MD
  Christina L. Master, MD
  Roni L. Robinson, RN, MSN, CRNP
  Douglas J. Wiebe, PhD
  Douglas J. Wiebe, PhD
  Mark R. Zonfrillo, MD, MSCE,
• Kristy B. Arbogast, PhD, is from the Center for Injury Research and Prevention and the Division of Emergency Medicine at the Children’s Hospital of Philadelphia. Arbogast can be reached at arbogast@email.chop.edu.
  
  Matthew F. Grady, MD, is from the Sports Medicine and Performance Center at the Children's Hospital of Philadelphia. Grady can be reached at gradym@email.chop.edu.
  
  Christina L. Master, MD, is from the Sports Medicine and Performance Center at the Children's Hospital of Philadelphia. Master can be reached at masterc@email.chop.edu.
  
  Roni L. Robinson, RN, MSN, CRNP, is from the Sports Medicine and Performance Center at the Children's Hospital of Philadelphia. Robinson can be reached at robinsonr@email.chop.edu.
  
  Douglas J. Wiebe, PhD, is from the Center for Clinical Epidemiology and Biostatistics at the Perelman School of Medicine, University of Pennsylvania. Wiebe can be reached at dwiebe@exchange.upenn.edu.
  
  Mark R. Zonfrillo, MD, MSCE, is from the Center for Injury Research and Prevention and the Division of Emergency Medicine at the Children’s Hospital of Philadelphia. Zonfrillo can be reached at zonfrillo@email.chop.edu.

full article here