by Prof Upendra M Chowdhary, MS, FRCS Edin & Glas) Consultant Neurosurgeon
The chronic traumatic encephalopathy (CTE) is now being recognised as a major topic for research and discussion among the doctors treating various groups of head injured patients. The long term damage to the brain was first published by Martland regarding people who were involved in boxing and the title of the paper was ‘Punch drunk’. Subsequently case report regarding dementia pugilistica was published. Recently, during the last 15 to 20 years, there, has been an explosive interest in chronic traumatic encephalopathy but most of the attention has been on repetitive minor head injury leading to CTE and most of research is related to brain injury produced during contact sports played in the American continent such as American football, professional wrestling, ice hockey, soccer and even cycling. But there is expanding literature available now in which one episode of moderately severe or severe head injury has been connected to early and more frequent onset of degenerative diseases akin to Alzheimer’s disease later in life.
In this discussion I am going to concentrate on the relationship between acute episode of moderate head injury and severe head injury to the development of neuro-degenerative diseases many years later (see below - Fleminger S, Oliver D, Lovestone S et al.). I have published an article entitled, “Chronic Traumatic Encephalopathy: A Medicolegal Perspective” in the summer 2017 issue of The Expert Witness, vol. 1; issue 20. In that article I had discussed the Epidemiology, Pathophysiology and clinical effects of Chronic Encephalopathy arising due to multiple repetitive concussive injuries to the Brain. In this article my aim is to discuss CTE arising from one episode of moderate head injury and due to severe head and brain injury.
Pathogenesis and pathophysiology:
With the acute severe head injury there are certain pathological changes that happen both during the acute stage and subsequently in a more chronic setting. The acute brain injury leads to petechial haemorrhages deep in the brain parenchyma, cortical and sub cortical haemorrhagic contusions, cerebral surface contusions and laceration of brain which shows up as traumatic subarachnoid haemorrhage and as focal damages in various parts of the cerebral hemispheres and even in the midbrain at the initial CT brain scan which is usually done within a few hours of the acute head and brain injury.
In addition to the damage directly sustained by the cerebral parenchyma and in some cases also that to the brain stem one has to add the two types of extra axial but intracranial haematomas that occur in a substantial percentage of patients with severe head injury and these are - (i) acute extra dural haematoma which compresses the brain and shifts that cerebral hemisphere to the opposite side (ii) acute subdural haematoma which produces similar structural changes. If the patients is very severely head injured then such patients may have trans-tentorial coning in which the mid brain is pushed against the tentorial edge on the opposite side giving rise to damage to the mid brain and this may produce prolonged unconsciousness and even persistent vegetative state.
The microscopic changes that takes place in the cases of severe head injury (also in moderately severe head injury) are related to other pathological processes such as wide spread vasoconstriction due to blood products in the CSF and blood products in the brain parenchyma itself plus cerebral oedema in cases of diffuse axonal injuries. In addition such patients are much more likely to have early/late onset epilepsy which would causes further ischemic damage.
Patients with moderately severe and severe head injury or moderately severe head injury have a CT brain scan within hours of being admitted to a hospital. This is adequate for the initial management of such patients and points towards guidelines about monitoring and physiological support.
MRI scan of the brain in the acute stages are seldom performed in the NHS because of logistical and financial problems and non-availability of MRI scan during emergency hours. But it has now been demonstrated that if the MRI scan of the brain is done in such patients even 6 months or a year later a considerable amount of pathological changes can be shown on the MRI scan which would point to the persistence of cerebral parenchymal and brain stem injuries even after a long period from the date of the accident. Such specialised MRI scan which uses specialised protocols such as diffusion tensor protocol etc. shows not only haemosiderin deposit but would also show white matter searing effect which clinically is known as diffused axonal injury.
All this means that there is now investigation available, which will show, within a period of 6 months to couple of years after the acute head injury, all the residual injuries that have had happened in the brain parenchyma itself at the time of the impact. In addition the MRI scan will show atrophy either focal or more generalised due to severe damage to the neuronal and glial cells. Up to here the pathogenesis and pathophysiology are known but it has not been firmly established, as yet, what happens, in such patients, in pathological terms, who develop chronic encephalopathy many years later and in an increased number but the consensus of opinion is that the ultimate pathology is similar but not identical to what happens in patients who develop CTE after multiple repetitive concussive or sub concussive injuries.
There are also some subtle differences in the clinical presentation between onset of CTE due to repetitive mild head injury and CTE produced many years after an acute moderately severe or severe brain injury. Whereas the former group of patients develop slowly progressive symptoms mostly starting with personality disorders and behavioural problems, the latter group of patients show clinical picture similar to but not identical to late onset Alzheimer’s disease.
A paper by B L Plassman et al. published in Neurology has stated as conclusion, “Moderate and severe head injury in young men may be associated with increased risk of Alzheimer’s Disease and other dementia in late life”. A paper published by S Fleminger et al. in The Journal of Neurology, Neurosurgery and Psychiatry has stated as conclusion, “This study provides support for an association between history of previous head injury and risk of developing Alzheimer’s disease”. This was a meta-analysis type of paper and has reviewed 15 studies related to this subject.
A paper published by Dr Sharon Shively et al. in Archives of Neurology in 2012 has stated in the abstract, “The best data indicates that moderate and severe traumatic brain injuries increase the risk of dementia between 2 and 4 fold”. Further on in this paper the authors have stated the following – “Traumatic brain injury is perhaps the best established environmental risk factor for dementia. It was estimated that individuals who had had a head injury of sufficient severity to result in loss of consciousness were at approximately 50% increased risk of dementia compared with others where there was no such injuries”. The paper further states, “The veterans who had sustained a severe traumatic brain injury were more than 5 times likely to have dementia compared with controls, while those who had sustained a moderate traumatic brain injury were at more than double the risk compared to the controls.” The paper further stated, “One of the most feared consequences of traumatic brain injury is dementia. Epidemiological studies indicate traumatic brain injury in early to midlife is associated with increased risk of dementia in late life, in the range of 2 to 4 fold compared with the general population”.
A paper published by Steven T DeKosky et al. in Nature Review Neurology in 2013 has stated under the heading of ‘key points’ the following – “Brain pathology after single incident of severe traumatic brain injury is similar to early amyloid pathology in Alzheimer’s Disease whereas repetitive traumatic brain injury can produce tauopathy with or without amyloidosis”. The author states later in the paper the following, “As the late consequences of traumatic brain injury generates pathology that is reminiscent of Alzheimer’s disease or pure tauopathy, reposit that these two disorders have a shared pathogenesis”.
In a paper published by Brent E Masel et al. in Journal of Neurotrauma has stated – “Traumatic brain injury increases long term mortality and reduces life expectancy. It is associated with increased incidence of seizures, sleep disorders and degenerative diseases, neuroendocrine disorder and psychiatric diseases”.
A paper published by James A Mortimer et al. in Neurology in 1985 with the title of ‘head injury as a risk factor for Alzheimer’s disease’ has stated in their abstract, “The findings suggest a possible etiological role of head injury in dementia of the Alzheimer’s type. It also states that the range of times of head injury and dementia spans several decades”.
Clinical and Medicolegal perspective:
The epidemiology and the pathology of CTE, after one episode of moderately severe or severe head injury, has now become established and is being accepted in neurosciences, neurological and neurosurgical spheres. Because this particular subject related to severe brain injury started to attract attention during the last 10 to 15 years or so in contrast to the subject of CTE arising from multiple repetitive concussive brain injury which dates back at least 25 to 30 years or more there is still only limited information available regarding the clinical importance of this knowledge about the CTE in severely brain injured patients. But some factors need to be noted as explained above. It is now accepted among the neuroscientists working on this subject that in moderately severe head injury and severe head and brain injury the increased risk of dementia is between 2 and 5 fold in contrast to the same age and sex cohort where there has not been any head injury.
The medicolegal question that arises is whether a more precise interval between the acute head and brain injury and the onset of dementia can be achieved or not. The simple answer is that it is not possible to give a precise number of years but what can be stated is that a significant of number of patients with moderately severe or severe brain injury will develop dementia akin to Alzheimer’s disease some 20-30 years after their head injury which will be earlier than the general population without the head injury who develop senile dementia or Alzheimer’s disease but have not had a head injury. It is now accepted that the CTE arising from one episode of severe brain injury is a fact of clinical medicine and that this happens 2-5 times more often (2-3 fold more in moderately severe brain injured patients and 3-5 fold more in severely brain injured patients) and that this needs to be kept in mind during a long follow up of the severely brain injured patients who have achieved initially enough recovery to be ambulant and at least able to live in the family and social surroundings with some support but are not in a minimally conscious state and are not in a vegetative state.
It will be interesting to see how the medicolegal and the legal profession takes up this subject towards the pounds and pence of compensation in the coming years, but not being a legal person I am not able to give an opinion on this precise subject. I would also like to add that severe and moderately severe traumatic brain injury in children, especially up to mid or late teens should be considered as 3 to 5 times more likely to develop CTE much earlier than their cohort of the same age and sex who had not had any head injury. This is because of the fact that their life span from the time of severe brain injury say in preteen or mid teen years would be much longer than a middle aged person sustaining similar traumatic brain injury.
1.Upendra M Chowdhary. Traumatic Encephalopathy: A Medicolegal Perspective. The Expert Witness. Summer 2017, Vol 1, Issue 20; 73-76.
2. Dekosky S, Blennow K, Ikonomovic M et al. Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers biomarkers; Nat Rev Neurol. 2013 April; 9(4): 192-200.
3. Fleminger S, Oliver D, Lovestone S et al. Head injury as a risk factor for Alzheimer’s disease: the evidence 10 years on; a partial replication. J Neurol Neurog Psychiatry 2003; 74:857-862.
4. Plassman B, Havlik R, Steffens D et al. Documented head injury in early adulthood and risk of Alzheimer’s disease and other dementias. Neurology; 24 October 2000, vol. 55 no. 8 1158-1166.
5. Massel B and DeWitt D. Traumatic Brain Injury: A Disease Process, Not an Event. Journal of Neurotrauma. August 2010, 27(8): 1529-1540.
6. MortimerJ, French R, Hutton T et al. Head injury as a risk factor for Alzheimer’s disease. Neurosurgery. February 1985, vol. 35, no. 2: 264.
7. Shively S, Scher A, Perl D et al. Dementia Resulting From Traumatic Brain Injury. Arch Neurol. October 2012; 69(10): 1245-1251.
Prof Upendra M Chowdhary,
MS, FRCS Edin & Glas)
Contact address for the author