Chronic Traumatic Encephalopathy ina National Football League Player (2006)

To the Editor: We appreciate the response from Omalu et al. (6) to our original Letter to the Editor regarding the article "Chronic Traumatic Encephalopathy in a National Football League Player" (1). After much consideration of their arguments, as well as those of the reviewers, we are still troubled by key problems and new information that underscore the need for Omalu et al. to fully disclose all information and to present unbiased data before presenting "scientific" conclusions. In their reply to our letter (6), Omalu et al. refer to another case of an "NFL player with similar neuropathological changes." Presumably, they are referring to the case ofTerry Long. Unfortunately, they failed to mention important information about this case. In January 2006, Drs. Wecht and Omalu announced to the press postmortem findings of a second football player, Mr. Terry Long, who they concluded died from repeated football-related head injuries. But, a revised death certificate, which was never released publicly, lists Mr. Long's cause of death as a result of drinking antifreeze. Ethylene glycol ingestion damages the brain and certainly clouds the pathologist's original conclusions. The conclusion that the ingestion of antifreeze was related to depression from repeated head injuries is, at a minimum, speculative. We think that the reporting of the Terry Long autopsy results and other examples cited below substantiate our concerns that Omalu et al. (5, 6) omit important data that readers need to make informed decisions, and that their original article reaches conclusions that cannot be relied upon. Omalu et al.'s (6) reply to our letter continues the pattern of factual inaccuracies and important omissions that characterized their original article (5). Omalu et al. state that the absence of a cavum septum pellucidum (with or without fenestrations) does not preclude the diagnosis of chronic traumatic encephalopathy (CTE) because "Corsellis and others have never asserted that this finding is a sine qua non of dementia pugilistica" (6). Omalu fails to include the fact that all of Corsellis' cases had an abnormality of the septum pellucidum (2). Two of the original 15 patients had died of recent cerebral hemorrhage that might have affected the septal region, so Corsellis did not include their cava in the final results. All of the remaining 13 patients had abnormalities of the septum pellucidum (12 cava with or without fenestrations, one fenestrated septum without a cavum) (2). This stands in stark contrast to Omalu et al.'s case, which had no abnormalities of the septum (5). Certain reviewers indicate that the nature of head injuries is very different in football than in boxing and suggest that we were essentially comparing apples and oranges (3, 4). We agree that there are significant differences between head trauma sustained in the two sports. The reviewers suggest that, because of these differences, chronic encephalopathy in football players would be expected to be different from that seen in boxers. This assumes that there is a chronic encephalopathy of football players. It seems that the end result of the difference we measured in head impacts sustained in the two sports (9) could be that there is no chronic encephalopathy in football players. In another attempt to demonstrate that their findings are similar to Corsellis' results, Omalu et al. then states that "our case showed degeneration of the substantia nigra and, most importantly, widespread neocortical neurofibrillary tangle formation" (6). This statement is also inaccurate. With regard to "degeneration of the substantia nigra," Omalu et al. failed to mention that every one of Corsellis' cases with loss of pigment and neuronal dropout in the substantia nigra also had neurofibrillary tangles (NFTs) in some or many of the remaining neurons in the substantia nigra (2). This stands in clear contrast to Omalu et al.'s case, which had no NFTs in the substantia nigra (5). With regards to widespread NFT formation, Omalu et al.'s choice of words in their original report is not the same as in their reply to our correspondence. In the abstract and body of their original article, Omalu et al. referred to their finding of "sparse neurofibrillary tangles" (5, p 130). The word "widespread" does not, in fact, appear in their original article. In their reply to our letter, Omalu et al. have replaced the word "sparse" with the word "widespread," seemingly adopted from our letter. The problem with this substitution is that "sparse" and "widespread" do not mean the same thing. The adjective "widespread" is used to describe the occurrence of a phenomena in an area in two ways: 1) how it is distributed over the area, in which case it means that it occurs in many regions of the overall space, and 2) the density with which it is seen in the areas, in which case it is synonymous with the words "prevalent," "common," and "pervasive" (8). Remaining consistent with Corsellis' original description, we were clearly using "widespread" in its broadest sense to describe a pattern of numerous NFTs seen in many areas of the brain. It remains unclear to us how Omalu et al. are using the word in their reply to our letter. Are they replacing "sparse" with "widespread"? If so, they need to clearly state that they are revising their original report of meager, few NFTS (synonyms for "sparse") and are now stating that NFTs occurred frequently and commonly in their material (8). If that were the case, it would lead us to question the accuracy of the original neuropathological descriptions. Or, are they using "widespread" and "sparse" together to describe their findings? If they are using "widespread" only to describe the distribution of NFTs in many areas of the brain and "sparse" to describe the meager numbers of NFTs seen in these areas, then they are really stating that the occurrence of NFTs was few and far between, infrequent and scattered, in their material. This description is obviously not at all consistent with Corsellis' report of "an abundance" of NFTs and a "vast" number of neurons with NFTs (2). Omalu et al.'s adoption of the word "widespread" in their reply thus serves to further confuse, rather than clarify, the issues surrounding our points of concern regarding their original report. Omalu et al. also write that "this pattern of neurofibrillary tangle formation would cause most neuropathologists to question whether the patient had a history of boxing and lead them to examine the clinical history for episodes of repetitive head trauma" (6). There are no citations or references given for this statement, and we think our findings further compromise the validity of the statement. Omalu et al. also write that their case had "deposits of B/A4, which were also seen in 19 of 20 cases of dementia pugilistica," citing Roberts (7) as their reference. Once again, they failed to mention a critical point about these 20 cases: 19 of the 20 had a cavum septum and the 20th was a man with very limited exposure to boxing (fewer than 10 bouts during a 2-year boxing "career") that the authors described as having "probable" Alzheimer's disease (7). This is another example of Omalu et al.'s omission of information that we think is important if the reader is to reach an informed conclusion. The reviewers who criticized us for bringing up the topic of CTE in boxers need to be reminded that it was Omalu et al. who tried to make the connection between their case and CTE in boxers. The entire first paragraph of the Discussion in their original article was devoted to reports of CTE in boxers (5). In this Discussion, Omalu et al. specifically mentioned the Corsellis study on "the neurohistological substrate in the brains of 15 retired professional and amateur boxers" (5). Omalu et al. referenced a number of other articles on CTE in boxers in their original report. If Omalu et al. had accurately presented the findings of Corsellis and others regarding the neuropathology of CTE in boxers, there would have been no need for us to object to their statements. However, if they had done so, it would have been obvious to the readers and reviewers that Omalu et al.'s case was not at all consistent with the CTE of boxers. Omalu et al. clearly thought that they needed to connect their case to CTE in boxers, or they would not have discussed it so prominently in their report (5). Any criticism for trying to link the findings in one football player to the neuropathology of CTE in boxers should have been directed at Omalu et al.'s original report, where we think it belonged. We are also concerned by Omalu et al.'s attempt to use an arbitrator's judicial decision to bolster their position (6). When did the courts become the arbiters of scientific truth? Legal opinions are irrelevant to scientific discussions in the forum of a medical journal such as Neurosurgery. In fairness to all of our colleagues, we think full disclosure of all facts by all parties is necessary for a full and open "scholarly discussion and understanding" regarding this important matter. We remain convinced that the authors should retract their paper or sufficiently revise it and its title. Ira R. Casson Elliot J. Pellman David C. Viano New York, New York