Prof Tute - Clinical Predictors Of Outcome In Abi

Clinical Predictors of Outcome in Acquired Brain Injury Professorial Tutorial Dr Sebastian Theilhaber, presented 13/05/2008

1. The Art of Prognostication

“It seems to be highly desirable that a physician should pay much attention to prognosis. If he is able to tell his patients when he visits them not only about their past and present symptoms, but also to tell them what is going to happen, as well as to fill in the details they have omitted, he will increase his reputation as a medical practitioner and people will have no qualms in putting themselves under his care.“ Hippocrates Ancient Greek Physician “Father of medicine” (* ca. 460 BC – † ca. 370 BC)

“Medicine is a science of uncertainty and an art of probability.” Sir William Osler Canadian born physician “Father of modern medicine” Inventor of journal clubs, bed side teaching and residency-ship (* July 12, 1849 – † December 29, 1919)

“Predictions are difficult, especially about the future.” “Yogi” Berra, (Laurence Peter) (* May 12, 1925) Base Ball player and manager One of only four players ever to be named “Most Valuable Player of the American League” three times.

2. Definition of ABI / TBI •

Acquired brain injury means, depending on the source, the traumatic event to the brain. It may also refer to the mechanism of injury. The use is not consistent and there does not seem to be a universally agreed definition.

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In Australia commonly used definitions are: 1. “Acquired brain injury (ABI) refers to any type of brain damage that occurs after birth.” [1], and 2. “Brain injury includes a complex group of medical and surgical problems that are caused by trauma to the head.” [2] This leads to inconsistent exclusion / inclusion of pathologic entities such as MS, Alzheimer, CVA, intracerebral bleeding secondary to ruptured aneurysm, Huntington's disease.

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[Better Health Channel] “Acquired brain injury”

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[Brain Foundation Australia] “Acquired Brain Injury”

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3. Epidemiology According to a comprehensive survey, done by the Center for Disease Control and Prevention's National Center for Injury Prevention and Control, the following annual statistics apply in the United States [3] (Population estimation 2008: 304 million [4]): At least 1.4 million people sustain a TBI. •

Approximately 50,000 people die from a TBI.

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Approximately 475,000 TBI's occur among infants, children, and adolescents aged 0-14 years.

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About 80,000-90,000 people experience the onset of a long-term disability due to a TBI.

The following groups are at particular risk for TBI: •

Males / females = 2 / 1 ratio to sustain a TBI.

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Highest risk for a TBI: Infants and children aged 0-4 and adolescents aged 15-19 years.

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Highest rates of TBI-related hospitalization and death: Adults aged 75 years or older.

Mortality rates after brain injury are highest in people with a severe TBI. In the first year after a TBI, people who survive are more likely to die from seizures, septicemia, pneumonia, digestive conditions, and all external causes of injury than are other people of similar age, sex, and race. However, the mortality rate after severe TBI has decreased since the late 20th century.

4. Pathophysiology For the purpose of this tutorial, the following simplification may be allowed: •

Primary Injury [5]: 1. Direct impact and damage 2. Acceleration-/deceleration injury (shear-, tensile- and compressive-strains, causing intracranial haematoma, diffuse vascular injury, or injury to cranial nerves) 3. Diffuse axonal injury (DAI: microscopic axonal damage, often not visible on imaging studies, caused by rotational acceleration. This is poorly understood but appears to be quite significant.)

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Secondary Injury [5]: Within hours or days after the event as impairment of cerebral blood flow, resulting in: 1. local edema, 2. haemorrhage, 3. increased intracranial pressure, 4. inflammatory response. This may cause cellular ion pumps to fail, the excessive release of glutamate and aspartate, free radical formation, proteolysis, and lipid peroxidation, all of which are believed to cause neuronal death.

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Langlois JA, Rutland-Brown W, Thomas KE. Traumatic Brain Injury in the United States: Emergency Department

Visits, Hospitalizations, and Deaths. Atlanta (GA): Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; January 2006. 4

[US Census Bureau]

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[emedicine] “Management and Staging of Traumatic Brain Injury”, Percival H Pangilinan

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Pathophysioloical pathways of primary and secondary injury

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5. Classification

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6. Concepts of Recovery from TBI In the shadow of the influential statements of the Nobel prize winner Santiago Ramón y Cajal's (picture, * 1st May 1852 - † 17th October 1934) forceful statement that regeneration of the adult brain after development was completed, was almost impossible, it had been commonly assumed until the 1960ies, that neuro-rehabilitation merely was a compensation, strategic behavioural tricks of the injured person to overcome their deficits. The assumption was that substantial reorganization did not occur, therefore no real recovery and structural changes found in the adult brain by neuro-anatomists of the time were interpreted as artifacts of histological techniques. With the work of Geoffrey Raisman it was demonstrated in 1969 [6] that those artifacts indeed represented characteristics of neuronal repair. This was possible due to the availability of electron microscopic techniques. He was able to demonstrate the reoccupation of severed, “vacant” synapses by surviving, other axons. He also demonstrated, that this led to a change in the delivered neurotransmitters of the synapse. Although studies had existed since the 1920ies, hinting towards the capacity of recovery, his results and similar ones were commonly interpreted as anomalies and that tests used simply did not detect the deficits underneath the functional compensation. A possible explanation for this tendency may be that the whole concept of neuroplasticity (or recover) can be seen as a challenge to the established concept of “localization of function”, which implies a genetic determination of neuronal populations. The idea of compensation/substitution rather then restitution needs to assume that remaining, healthy, surrounding tissue modulates its physiologic activities to facilitate the compensation, which, in itself, appears somewhat contradictive to the strict concept of “localization of function”. However, a growing number of scientists seems to think that the existence of recovery cannot be denied although the precise circumstances under which it occurs, are unknown yet. A significant clinical consequence of this understanding is the need for neuro-protection and optimization of neuro-rehabilitation, particularly in the early recovery stages. In very early injury the underlying mechanisms are even more disputed. This is referred to as Equipotentiality, which is the capacity of an anatomically distinct area to serve a variety of functions. This capacity is believed to be significantly better the younger the brain is. The unexpected “sparing of functional loss” in later (for the associated damage) has been formulated as ”Kennard Principle”. However, research has also shown that there is a critical “period for plasticity”, where injury leads to a much worse outcome then if an injury occurred only weeks to months later. This was demonstrated by Brian Kolb et al. The concept of “vicariation” is the assumption that even the mature brain has a number of redundant systems to facilitate the “takeover of function” needed for compensation. It was found that this cortical remapping is highly variable and individual. It was also found that serial damage was much better compensated when some time of remapping was allowed, even if the then functional area was removed. The more “chronic” the process, the better the outcome. In general there seems to be the capacity to “mirror” and – partially – reorganize the lost areas function in associated cortex, often across hemispheres. This seems to be related to the more recently substantiated concept of “diaschisis” (Eng: "shocked throughout"), that was initially formulated by Constantin von Monakow (1853-1930, Russian-Swiss neuropathologist) at around 1914, which states that brain injury triggers a long lasting inhibition of neuronal activity. It is now known, that injury induces biochemical and genomic alterations in protein production through which synapses in the damage area are removed and that this effect takes place to some degree in the – intact – contralateral homologues area as well.

[Source Picture, Cajal]

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Raisman G, Neural Plasticity in the Septal Nulei of the Adult Rat; Brain Research, 14: 25 – 48, 1969

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7. Neurodiagnostic Technical neurodiagnostic of all kinds is, of course, the basis for the much of the outcome-assessment. It provides the non-clinical assessment , which is not the focus of this tutorial. Therefore it may be allows to merely mention the most important techniques used: •

Static imaging, such as CT and MRI

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Functional imaging, such as SPECT, PET, FMRI,

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Electrophysiological assessments, such as SEP (somatosensory evoked potentials), BAEP (brainstem auditory evoked potential), EEG, P250 (pain related potentials), P300 (event related potentials).

8. Classification of Severity- and Prediction- Tools for TBI

Age: Provides a very basic prognostication about outcome. See “9. Prognosis and Outcome”.

Glasgow Coma Scale: Provides a basic prognostication about the outcome of an TBI.

The GCS is the widely used tool to grade the severity of TBI:

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GCS scores between 13 and 15:

define mild brain injury,

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GCS scores between 9 and 12:

define moderate brain injury,

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GCS scores between 3 and 8:

define severe brain injury [7].

[Kaplan & Sadock's Comprehensive Textbook of Psychiatry, 8th Edition] “Neuropsychiatric Aspects of Traumatic Brain Injury”, pg 391

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Loss of Consciousness: (LOC): The duration of LOC is another commonly used tool and thought to be of higher predictive value.

PTA (Post traumatic amnesia): The duration of PTA is the period that elapses between the time of injury and the restoration of continuous memory for day to day events, which clearly relates to the GCS and is often characterized by: •

Confused speech

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Pseudo-psychotic symptoms

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Perseveration

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Elated mood

The severity of PTA is defined as: PTA

1 – 4 hours

mild brain injury

PTA

4 – 24 hours

Moderate brain injury

PTA

> 1 – 7 days

Severe brain injury

PTA

> 1 – 4 weeks

Very severe brain injury

PTA

> 1 – 6 months

Extremely severe brain injury

PTA

> 6 months

Chronic amnesia state

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Westmead PTA Scale: This test is the preferred tool in Australia.

PROTOCOLL: The Patient should be alert as possible, there should be no distractors or no clues. Make sure you know the correct answers to all the items on the scale. One or no point for each item. In case of no spontaneous or insufficient response (“I don't know.”), ask the same question again, offering three choices.

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Question 1: HOW OLD ARE YOU ? The examiner must ask for clarification if the patient states, for example, that they will be '30 next year'. The acceptable alternatives are: 'So that makes you how old at the moment ?' or 'How old are you now ?'. Question 2: WHAT IS YOUR DATE OF BIRTH ? If the patient has difficulty with the concept of 'date of birth', it is permissible to ask 'When is your birthday ?', and then follow with 'What year were you born in ?'. Question 3: WHAT MONTH ARE WE IN ? For emphasis the examiner can ask what month are we in now ? The patient must name the month. For example, if the patient answers 'the 6th month', the examiner must ask the further question 'What is the 6th month called ?'. Question 4: WHAT TIME OF DAY IS IT ? (MORNING, AFTERNOON OR NIGHT) The patient should answer with one of the 3 choices given in the question. Question 5: WHAT DAY OF THE WEEK IS IT ? The examiner may add for the sake of emphasis 'What day of the week is it today ?'. Question 6: WHAT YEAR ARE WE IN ? It is considered correct for patients to answer in the short form '95', instead of '1995'. Also, an acceptable alternative prompt (for the rest of the 1990s) is 'The year is 19 what ?'. Question 7: WHAT IS THE NAME OF THIS PLACE ? The patient has to be able to give the name of the hospital. For example: Westmead Hospital. (NB: The patient does not get any points for just saying 'hospital'.) If the patient can not name the hospital, give them a choice of 3 options. To do this pick 2 other similar sized hospitals in your local area or neighbouring region. In Westmead Hospital's case the 3 choices are 'Nepean Hospital, Westmead Hospital or Liverpool Hospital'. If the patient does not spontaneously answer the question, the examiner should re-ask the question and say 'Are you at home, a hospital or a hotel ?'. If the patient correctly answers this first part, follow with the question: 'What is the name of this hospital ?'. (Do not ask this question if the patient said 'home' or 'hotel'.) If the patient can not spontaneously answer give them the choice of 3 options, 'Is it Nepean Hospital, Westmead Hospital or Liverpool Hospital ?'. (NB: The patient must answer both parts of this question correctly to score 1 point.) Question 8: HAVE YOU SEEN MY FACE BEFORE ? All this question requires is a simple yes / no answer. An acceptable alternative is 'Have you seen me before ?'. Even if the patient answers 'no' to this question, you should still ask Question 9. Question 9: WHAT IS MY NAME ? If the patient fails to respond spontaneously a choice of 3 names is given. They should start with the same letter and have the same number of vowels. For example: 'Lisa, Linda or Lesley'. Question 10: WHAT WERE THE 3 PICTURES THAT I SHOWED YOU YESTERDAY ? If the patient can not spontaneously recall the picture cards, there are 2 acceptable presentation modes: (1) Showing all 9 cards to the patient, one at a time; or (2) Laying all 9 cards out on a table. In both cases the patient must pick the 3 target cards either by saying 'yes' / 'no' or by pointing. The patient may also spontaneously recall 1 or 2 cards and then need to use one of these presentation modes to pick the remaining target cards. Score 1 point for each card that is correct. (NB: The position in which the cards are placed or presented should vary each day.) Scoring and Picture Cards: Write down the patient's answer in the box and score 1 for correct and 0 for incorrect in the box underneath. This is done so that an exact record is kept of what the patient has said. (Perhaps a pattern may emerge if a patient continually gets an item wrong.) Remember that no half marks can be given. When a patient does not spontaneously answer a question (i.e. when a choice of 3 options is given for a question or when one of the 2 presentation modes for the picture cards is given) place an asterisk next to the answer box. This will show that this question was administered differently from the others. The other important rule you have to know is that when the patient scores 12 out of 12 you must change the picture cards. You can pick the cards for the patient, or, as some examiners do, turn the cards over (blank side up) and let the patient pick the 3 cards. Record the new cards and the date they were chosen on the Form. (A set of cards is regarded as different from the previous set if at least one of the cards is changed. If the patient or examiner manages to again pick the same 3 cards they must pick all the cards again.) Rehearsing with the Patient: At the end of testing you need to rehearse with the patient. That is, before leaving the patient you must correct their mistakes, tell them what they have to remember for tomorrow and check whether they have encoded it properly. Step 1 is to go through the incorrect items with the patient e.g. 'John you got a couple of items wrong: today is Monday; and it is morning.' Step 2 is to remind the patient what they have to remember for tomorrow. (This is also the time to introduce the patient to the new picture cards if they have scored 12 out of 12.) Show the 3 picture cards and go through them with the patient. Then say, 'John I will be coming to 9 / 12

see you tomorrow and I want you to remember my name - Lesley - and the 3 pictures I have shown you - Bird, Flower and Cup.' Step 3 is to check whether the patient has encoded the memory items properly. To do this you need to distract the patient for 1 to 2 minutes with some idle conversation e.g. 'What is your favourite TV show ?', 'What is your favourite sport ?' or 'What did you have for breakfast, lunch or dinner ?'. Then ask the patient what they have to remember for tomorrow. Tell the patient whether they were right or wrong and correct any mistakes. Then prior to leaving, show the patient the 3 picture cards again and say, 'John, I want you to remember my name - Lesley - and the 3 pictures I have shown you - Bird, Flower and Cup.' The testing is stopped when a perfect score of 12 is achieved for 3 consecutive days or on advice of the Clinical Neuropsychologist.

GOAT (Galveston Orientation and Amnesia Test): The GOAT is similarly to the Westmead is designed to assess orientation and amnesia, at should be done at least once a day. Score of 78 or more on three consecutive occasions is considered to indicate that patient is out of post-traumatic amnesia (PTA).

PTA is believed to have ended, where tests are being scored accordingly or disorientation and amnesia persists beyond six months, after which coma is unlikely to remit

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9. Prognosis and Outcome Age: •

Older age is associated with worse outcomes

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Threshold values are: •

Good recovery is unlikely when greater then 65 years

GCS: •

Lower scores are associated with worse outcomes

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NO threshold values

LOC: •

Longer duration is associated with worse outcomes

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Threshold values are: •

Severe disability is unlikely when less then two weeks

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Good recovery is unlikely when greater than four weeks

PTA: •

Longer duration is associated with worse outcomes

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Threshold values are: •

Severe disability is unlikely when less then two months

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Good recovery is unlikely when greater than three months

Neuroimaging: •

Certain features (such as depth of lesion) are associated with worse outcomes

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Threshold value is: •

Good recovery is unlikely when bilateral brainstem lesions were present on early MRI

10. Relevance for Psychiatric Practice Can be the whole spectrum of psychiatric disorders [8], such as: •

Delirium

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Mood disorders, especially depression

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Psychotic disorders, from mild delusional believes to schizophreniform psychosis.

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Anxiety disorders, such as PTSS, generalized anxiety, OCD

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Personality changes similar to PD's

11. Take Home Message •

Almost any mental illness can be due to brain injury.

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Brain injury does not necessarily impress as an dramatic event.

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Similarly, the neuropsychiatric symptoms maybe subtle.

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Psychiatry is closer to Neurology then they think.

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There are Nobel prizes to be won...

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[Kaplan & Sadock's Comprehensive Textbook of Psychiatry, 8th Edition] Ch 2.5; Neuropsychiatric Aspects of Traumatic Brain Injury, pg 390

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12. Other Literature Used: •

Brain Injury Medicine: Principles and Practice, By Nathan D. Zasler, Douglas I. Katz, Ross D. Zafonte; Published 2006, Demos Medical Publishing, LLC; 1275 pages; ISBN:1888799935

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The American Psychiatric Publishing Textbook of Neuropsychiatry and Behavioural Neuroscience; By Stuart C. Yudofsky, Robert E. Hales; Published 2007 American Psychiatric Pub, Inc.; 1332 pages, ISBN:1585622397

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Textbook of Traumatic Brain Injury, By Jonathan M. Silver, Thomas W. McAllister, Stuart C. Yudofsky; Published 2005, American Psychiatric Pub, Inc.; 771 pages, ISBN:1585621056

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Traumatic brain injury, John Olver, MBBS, MD, FAFRM, is Associate Professor, Monash University, and Director of Rehabilitation, Caulfield General Medical Centre and Epworth Hospital, Victoria. Australian Family Physician Vol. 34, No. 4, April 2005

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Systematic review of prognostic models in traumatic brain injury; Systematic review of prognostic models in traumatic brain injury; Pablo Perel, Phil Edwards, Reinhard Wentz and Ian Roberts; BMC Medical Informatics and Decision Making 2006, 6:38

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Traumatic Brain Injury: Rehabilitation for Everyday Adaptive Living, By Jennie, pg 51, Published 1995 Psychology Press, ISBN:0863773761

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Traumatic Brain Injury, Merck Manuals, 18th ed

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Management and Staging of Traumatic Brain Injury, Percival H Pangilinan; eMedicine

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