By John W. Henson, MD, FAAN, AAN.com Science Editor
Researchers at Boston University School of Medicine's Center for the Study of Traumatic Encephalopathy reported on January 28 the results of an autopsy study on former National Football League (NFL) player Tom McHale. McHale died at age 48 after reportedly struggling with major psychological issues. McHale's autopsy brings to six the number of autopsied brains of former NFL players who have shown the neuropathological findings of chronic traumatic encephalopathy (CTE). Some of the cases, including McHale's, have yet to be published. AAN.com asked several experts to comment on these findings.
Ann McKee, MD, Associate Professor of Neurology & Pathology at the Boston University School of Medicine, has served as Director of the Neuropathology Core of the BU Alzheimer’s Disease Core Centersince its inception in 1996.
AAN.com: What are the neuropathological features of CTE? Are the findings specific for this disorder? Do the findings suggest a diffuse process or do they congregate around areas of frank injury?
McKee: Chronic traumatic encephalopathy is a progressive tauopathy characterized by extensive tau-immunoreactive neurofibrillary tangles, astrocytic tangles, spindle-shaped and threadlike neurites throughout the brain. The neurofibrillary degeneration of CTE is distinguished from other tauopathies by the preferential involvement of the superficial cortical layers, the irregular, patchy distribution in the frontal and temporal cortices, the propensity for sulcal depths, the prominent perivascular, periventricular and subpial distribution, and the marked accumulation of tau-immunoreactive astrocytes. Deposition of beta amyloid, most commonly as diffuse plaques, occurs in fewer than half the cases. Initially we believe the tau related changes may be found focally and are most likely related to the area of injury. However, as the disease progresses it appears that a pathological cascade is triggered that sets off a neurodegenerative process involving deeper structures of the brain, particularly the amygdala, hippocampus, thalamus, mammillary bodies, and other components of Papez circuit.
AAN.com: Does there seem to be any age specificity of the findings? In particular, can they be seen in younger people?
McKee: We have found the earliest changes in an 18–year-old high school student. Others have found changes in 20-plus-year olds. It is a progressive degenerative process: once set off, the longer an individual lives the more severe the changes.
AAN.com: Is there a proposed pathophysiological mechanism for the production of these changes by trauma?
McKee: I do not have an easy answer for that.
AAN.com: Are the findings of CTE related to a particular sport or mechanism of head trauma?
McKee: No. CTE appears to be related to repetitive concussive or subconcussive injury that can come about from any number of sports—boxing, football, wrestling, skiing, horseback riding, basketball, and swimming. CTE is also found in epileptics, and military veterans, for instance.
AAN.com: Do we have a sense of how closely the neuropathological features correlate with cognitive or psychological changes?
McKee: As the changes accumulate in the cerebral cortex, including inferior orbital cortex, amygdala, and hippocampus we see early behavioral and personality changes often accompanied by memory lapses.
Chronic traumatic encephalopathy is a serious concern to neurologists, who may have to deal with these issues. The American Academy of Neurology established a Task Force for the Prevention of Head Trauma in Recreational Activities of the Science Committee last year.
Ira R. Casson, MD, is an attending neurologist at Long Island Jewish Medical Center and co-chairman of the NFL Committee on Mild Traumatic Brain Injury.
AAN.com: What are the clinical features of chronic traumatic encephalopathy (CTE) and would you tell us in what situations this syndrome is thought to exist?
Casson: The clinical features of CTE in boxers include dysarthria, parkinsonian signs, cerebellar signs, and long tract signs. They also include the cognitive/memory impairments seen in dementia. The syndrome has long been known as pugilistic dementia. These clinical features may occur in varying severities combinations. Psychiatric signs such as paranoia, delusions and outwardly directed rage reactions have been seen, but suicidality and/or severe depression have not been a part of the clinical picture. This clinical syndrome has been reported in boxers and a few steeplechase jockeys.
AAN.com: Do you think that the syndrome of CTE, as described in boxers, can be extrapolated to other contact sports, such as football? Are there differences in the nature of head trauma in these sports?
Casson: It is not known whether or not the CTE of boxers can be extrapolated to contact sports such as football. There are numerous differences in the types of head impacts seen in football compared to those seen in boxing. Football players wear hard protective helmets with faceguards, whereas professional boxers do not wear any protective headgear during bouts. The soft headgear that some professional boxers wear while sparring—and amateur boxers wear during bouts and sparring—do not offer any protection for the brain. The major impacts to the head seen in professional football result primarily in translational accelerations, whereas those seen from punches of boxers result primarily in rotational accelerations. During sparring and actual bouts, boxers receive a very large number of blows to the head (after all, the purpose of the sport is to knock out the opponent by hitting him in the head), whereas professional football players receive a much smaller number of blows to the head.
AAN.com: Recent articles in the press have suggested the possibility that CTE has produced significant mental health problems among affected professional football players. How strong is the evidence for that assertion?
Casson: The evidence purporting to link the neuropathological findings in a small number of cases of retired football players to significant mental health problems (specifically severe depression, inability to hold a job, financial insolvency, suicidality) is very weak. Depression is a very common illness and its etiologies are multifactorial. Suicidality is also a very common problem with multifactorial etiologies. To label head trauma from football as the major or sole cause of these problems reflects an oversimplistic approach to these complicated conditions. The dominant feature of the neuropathology described in these six cases reportedly is the deposition of hyperphosphorylated tau proteins. Some have suggested that these tau protein deposits are the cause of depression and suicidality in these cases. However, if that were the case, why then are suicidality and/or depression not a part of the clinical picture of any of the myriad of tauopathy diseases that are well known to clinical neurologists? Why are depression/suicidality not a part of the clinical picture of boxers with CTE?
AAN.com: Is the extent or severity of the neuropathological changes in the six players described to date a cause for concern? If so, is the concern only at the professional level or could younger athletes be at risk too?
Casson: The six cases reported need to be presented to the medical/scientific community in the appropriate scientific forums (e.g., peer-reviewed medical journals, scientific meetings such as the AAN Annual Meeting) where experts in the field can have a chance to review and discuss all the findings.
Dr. Casson receives a stipend for his activities as co-chair of the NFL Committee on Mild Traumatic Brain Injury. In addition, he is on the speakers panel for GlaxoSmithKline, Pfizer Inc., and Teva Pharmaceutical Industries Ltd. Dr. Casson has also given expert testimony in accident cases within the past 24 months. Within the past five years, he has received research support from the National Football League for a clinical study on retired NFL players, for which he is a Lead Investigator.
Dr. McKee has nothing to disclose.
Dr. Henson has received personal compensation for consulting with GlaxoSmithKline within the past year. He receives compensation for serving as Associate Editor for Science, AAN.com.
Disclaimer: The opinions expressed in this posting are those of the author only and do not represent the views of the American Academy of Neurology or any of its affiliated subsidiaries.
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