by Professor Upendra Mohan Chowdhary
For several years now there has been intense media attention regarding athletes in contact sports developing, some years after their retirement, symptoms and signs of what can be loosely defined as dementia (1,4,12). A Hollywood film, entitled “Concussion” was made starring Will Smith in 1995 (8). This subject of athletes, in certain sports, developing delayed post retirement dementia has been known since 1928 when Martland in JAMA published an article which was entitled ‘Punch drunk’ (6). This was related to boxers exhibiting memory problem, behaviour and/or motor abnormalities and these symptoms had appeared several years after they had retired from their amateur or boxing careers. This was known to the relatives of the boxers, to the sport writers and the boxing fraternity and was referred to as ‘punch drunk’. Martland (6) was the first to put it into medical literature.
Subsequently as interest developed and more and more such cases came to be known, Millspaugh (9) wrote an article which was publish in the US Navy Medical Bulletin in 1937 where he coined the words ‘dementia pugilistica’. Millspaugh also studied the brain of some of these patients and differentiated these from other causes of neuro-degenerative disease such as Alzheimer’s Disease (AD), Parkinson’s Disease (PD) etc. Subsequently more and more attention came to be focused on athletes of other sports and even other professions where repeated head injury had happened ranging from minor head injury to major head injury. The association between athletes in a variety of sports, where close contact between athletes was a regular occurrence, were studied and this included players in American football, professional wrestling, professional ice hockey (both in Canadian and USA leagues), soccer, cases of repeated physical abuse, repeated epileptic seizures and head banging (4). During the recent years the media has publicised these cases especially the cases of famous professional athletes who had developed this delayed neuro degenerative disease. In modern times this came to be known as chronic traumatic encephalopathy (CTE). This description was first used by Miller et al. (11).
Most of the attention, both in the literature and in the media, was related to repetitive minor head injury causing concussion but in medical literature cases started to be published were one episode of moderately severe or severe injury, most of which were accident related, had also resulted in chronic traumatic encephalopathy (CTE) (3). One publication had tried to separate these two types of aetiology as acute and chronic traumatic encephalopathies (7). As the scientific and media related attention has mostly been focused on repetitive minor head injury leading to delayed CTE and as most of the publication and research has been directed toward this, I am only going to discuss this type of CTE related to repetitive minor head trauma, mostly in sports, where physical contact is common place but also related to one or two other aetiologies such as in Armed Forces personnel (10) both during training and during combat where they suffer from minor head injury or even moderate head injury mostly related to explosion of ammunition or of improvised explosive devices.
Most of the scientific studies and even media attention has been in the United States and is related to players in two of the most popular sports in the USA, which are American football and ice hockey. It is also worthy of noting that soccer has been also mentioned frequently in the literature. It is now apparent that CTE is now a worldwide disease and affects the athletes in the sports mentioned above but also in combat related injuries to Armed Forces personnel (3, 10) and even in abuse cases where there has been repeated trauma to the head. It is also worth noting that three of the players who played for England in the 1966 World Cup winning team have, by 2016, developed all these symptoms and signs of chronic traumatic encephalopathy. This means that out of the 11 players 3 have been affected. This is a very high percentage of professional soccer players being diagnosed as having chronic traumatic encephalopathy on clinical grounds. The surmise is that footballers who played regularly at amateur level or professional level in the 1960s and even in 1970s played with leather footballs that used to get very heavy when wet and it is postulated that the repeated heading of these balls produced damage to their brains, the clinical picture of which appeared as long as 40 to 50 years later.
American professional football players who died between February 2009 and June 2010 totalled 321 and the brain of 12 of these underwent detailed post mortem and neuropathological examination of their brains in Boston. It was suggested that the estimated life-time prevalence rate is at least 3.7%. This is a somewhat conservative estimate but still signifies enormous public health risk for a person who suffered repetitive mild trauma especially in the contact sports noted above (4). It is also to be noted that all over the world the various types of contact sports are played by a very large number of athletes and even if ultimately a small percentage of them develop chronic traumatic encephalopathy the public health implications are frightening.
Symptoms and clinical presentation
One of the important point to remember is that the chronic traumatic encephalopathy develops several to even 30-40 years after the athlete has retired from their career and hence they are in their 50’s or 60’s and a certain percentage of the population at around the same age group, but usually somewhat later, develops naturally occurring degenerative brain disease such as Alzheimer’s Disease, Parkinson’s Disease, amyotrophic lateral sclerosis etc. The clinical symptoms may overlap but various associated and circumstantial factors will have to be taken in to account to separate the CTE symptomatology from these naturally occurring neuro degenerative diseases (1). Two important factors have to be taken into account here, viz. (i) the definite history of repeated minor head injury during the younger years (ii) somewhat early onset of the symptoms of neuro degeneration related to the brain.
CTE is defined as progressive neuro degenerative syndrome caused by single, episodic or usually repetitive blunt force impact to the head and transfer of acceleration – deceleration and rotational force to the brain (1).
The latency period for most of the contact sports are at least 6-12 years after the athlete has retired from their playing era. In many such cases, especially boxing, the latency period could be double or even triple the estimate given above.
The symptoms usually are noted firstly by close relatives and friends of such patients and the difficulties are in personal interactions, business, behavioural and financial affair issues which may then progress to depression, alcohol or substance abuse or is likely to lead to progressive disorganisation of lifestyle. The symptoms of CTE have been divided into 4 broad categories related to these functions – behaviour, memory related functions, mood and motor functions (1). The behavioural changes in addition to what has been noted already could be anger related problems, aggressive and/or impulsive behaviour, impaired judgement which is associated with vastly increased rate of suicides in this group of patients (4). Subsequently short-term memory loss and learning difficulties arise and this may be associated with motor difficulties later on. This sequence of onset of symptoms in CTE differentiates it from Alzheimer’s Disease where the memory problem starts first.
Diagnosis of CTE
The clinical diagnosis of CTE is based on circumstantial evidence, onset of behaviour related problems as noted above in people who have history of repeated minor head injury in their younger days and this should give rise to strong suspicion of CTE. Unfortunately there are no well-established diagnostic criteria that have been accepted in the neurological world which will firmly diagnose CTE in a living patient. Standard MRI Scan may show fenestrated Cavum Pellucidum (5). There are some promising developments and it is likely that in the next 10 years or so a combination of very specialised MRI scanning and presence of biochemical markers resulting from the cerebral degeneration in CTE will become available to the extent that there can be confirmatory diagnosis of CTE. The specific protocol of diffusion tensor MRI scan and specialised functional MRI scanning is showing good potential to diagnose the CTE and differentiate it from the other neurodegenerative disease such as Alzheimer’s Disease and Parkinson’s Disease. But there are problems in these investigations which are that the neuroscientific community has not agreed that what are specific features in these specialised MRI scans to confidently diagnose CTE and as yet the biomarkers are also not that discriminatory between CTE and other types of neurodegenerative diseases.
Hence, the diagnosis is mostly based on clinical factors which are earlier onset of behavioural changes in persons who had defined history of repeated minor head injury in their younger days and who on MRI scan do not show typical pictures of Alzheimer’s Disease. There are differing patterns of tau related deposition in CTE and in Alzheimer’s Disease which are well known for Alzheimer’s Disease as typical findings and hence once in such patients Alzheimer’s Disease has been excluded then the diagnosis of CTE is very much more likely.
There is a consensus of opinion developing that CTE is a progressive disease (2) and the patient would continue to deteriorate and go through the four categories of neurological and psychological deterioration as noted already in this article. There no specific treatment for patients with CTE except for general supportive measures and treatment of the main disabling symptoms but they are not very effective and progressive deterioration is much more likely.
There is a possible genetic predisposition in the majority of these patients but again this has not been confirmed as it is not possible to do the genetic studies in every person who has multiple minor head injuries. One of the emerging genetic defects is related to ApoE4 allele (1).
One question that is frequently put to the neurological experts is – “Will nearly all football players develop CTE?” (12) The answer is that in strict neuroscientific terms we do not know the situation here but, the media reports have been somewhat frightening as one of them had stated that up to 96% of national league players in the USA and 79% of all football players are likely to develop CTE. The consensus of opinion, as noted by McKee and colleagues (7), has stated that there is not enough evidence in the literature to give a definitive answer to this question.
On the other hand it has been emphasised in almost every article published on this subject that as (a) there is a delayed period of 10 to 20 years or even longer after the athlete has retired and (b) that the true incidence will only become evident once the in vivo diagnostic criterias have been established and agreed. As this will take many years it is much better to concentrate on prevention. There has been a begrudging acceptance of CTE by the professional sports associations in the USA, which came about after several litigations, (8) against the American football and North American professional ice hockey associations and there have been some changes to the rules and stricter head to head contact rules in these sports.
There also has been some biomedical research going on regarding estimating the force applied in head contact by putting biosensors in the helmet and improving the design of the helmet. There has been pressure, in the United Kingdom, put on the boxing bodies, especially by the British Medical Association and by group of neurosurgeons and neuroscientists that professional boxing should be radically modified in various ways to reduce the risk of the boxers developing CTE in later life or even abolished. But, it seems that this advice is having very slow effect in the prevention aspects of injury during boxing.
There has been some debate whether not only repeated concussion but also sub concussion type repeated head and brain injuries are responsible for development of CTE. Concussion is defined as a temporary change to mostly the cognitive and behaviour pattern in a person who has sustained minor head injury. The symptoms are confusion, disorientation, temporary cognitive deficit, some temporary behaviour changes, dizziness, headache etc. (11). The definition of concussion does not include mandatory loss of consciousness but most of the patients suffering concussions have at least transient loss of consciousness. Sub-concussion has been defined as lesser head injury where the symptoms were even more transient and the recovery was faster.
Likely future development and research
The basic neuropathological research has been trying to get as much detailed histological work done on a large number of donated brains from such athletes after they have been clinically diagnosed to have CTE.
There is also effort being made to get some in vivo diagnostic criteria formulated and then get it approved in an international meeting. The last consensus CTE Meeting was in 2012 where some directions were given regarding future research. There is also research being done for estimation of biomarkers, both as can be detected by specialised MRI Scan and possibly also in blood. It is likely that the special protocol based MRI scan where individual chemical molecules can be scanned and functional MRI scan where in the earliest stages of behavioural changes depression and aggression in such athletes could be measured and defined and this may lead to establishment of criteria for MRI based diagnosis.
One of the reasons that I have decided to publish this article is to make the legal profession aware of this clinical syndrome of CTE. The CTE appears many years, even up to 20-30 years, after repeated mild head injuries, whether that be just concussion or subconcussion and that is recognised to be a different group of neuro degenerative diseases than well-known conditions such as Parkinson’s Disease, Alzheimer’s Disease and amyotrophic lateral sclerosis.
As literally millions of concussions and subconcussions occur not only in sports but in other circumstances (1.6 to 3.8 million sports-related concussions occur annually in the United States) (7) and as there has been enormous media attention on this subject it is likely that there will be legal claims that CTE has developed in a particular person due to the repeated concussions sustained during sports where personal contact is part of the game and that (a) this risk was not made known to that person and (b) preventive measures were not taken. Based on such premise there may be a claim made against a professional body, a school, a sports club, even colleges and universities and the Ministry of Defence in relation to combat related repetitive head injury. The subject from a medicolegal point of view is full of mine fields. This is mostly due to the difficulty in diagnosing CTE in vivo (in a living person) with certainty. The lack of definitive in vivo diagnosis of CTE has not been established. There are various circumstantial matters that would point strongly to CTE in contrast to other naturally occurring neuro degenerative diseases.
The other problem is that in-depth and comprehensive knowledge about this subject may be scarce as not only a very good knowledge of neurodegeneration is needed from such experts but they have to study in great detail the literature, especially the current literature as there are constant advances in the knowledge related to CTE.
As most of the cases of CTE happens 10-15 years earlier than the mean age for Alzheimer’s Disease or Parkinson’s Disease, if on legal basis CTE is confirmed to have resulted from repeated concussive minor head injury some 15-20 years earlier and as CTE is a progressive disease the monetary compensation is likely to be very substantial. On the other hand as has been repeatedly mentioned in this article the establishment of diagnosis of CTE is based mostly on circumstantial evidence, which has been discussed already in this article.
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