Comparison of Clinical Modalities to Detect Mild Traumatic Brain Injuries

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Abstract

Mild traumatic brain injury (mTBI) or concussion is a neurophysiological dysfunction caused by rapid acceleration or deceleration trauma to the head. The decreased cerebral blood flow and structural dysfunction occurs immediately after both TBI and mTBI. Depending on the severity, they can stay reduced for a long period. This reduced blood flow prevents oxygen and glucose supply to the tissue, leading to depressed metabolism. It is therefore necessary to immediately detect the post traumatic changes inside the brain to develop a suitable diagnosis to prevent post-injury symptoms and second impact syndrome. Therefore, the need to accurately identify and distinguish brain damages following mTBI is an absolute necessity.

Neuropsychological testing, CT and MRI are the standard techniques that is used in the detection of mTBI. However, there are several advantages and disadvantages for each technique and therefore it is important to choose a modality that provide detailed information about the injury. This could vary between individuals depending on the severity, age and type of injury. There are existing other modalities that could be potentially used for the detection of mTBI. This report analyses all the current and future modalities and technique that can be used for the detection of mTBI and compares them by identifying advantages and disadvantages of each technique. It also provides a brief description on the situation where one modality would be better than other. Comparison between neuropsychological and clinical modalities tests would be also be included in this report.

Contents

Abstract

Introduction

1. The Brain

i. Structure and Function of Brain

2. Mild Traumatic Brain Injury (Concussion)

i. Pathophysiology of Mild Traumatic Brain Injury

ii. Mild and Severe Traumatic Brain Injury Complications

iii. Symptoms of concussion

iv. Causes of concussion

v. Current treatments for concussion

3. Neuropsychological Ways to detect mTBI

i. What is neuropsychological testing?

ii. Neuropsychological Questionnaire

iii. Cognitive testing

iv. Motor and Balance Testing

4. Clinical modalities to detect mTBI

i. Magnetic Resonance Imaging (MRI)

ii. Computer Tomography (CT)

iii. Electroencephalogram (EEG)

iv. BIOMARKERS

v. Near Infrared Spectroscopy (NIRS)

vi. NUCLEAR MEDICINE (SPECT AND PET)

vii. ULTRASOUND

5. Comparison of Techniques that detect mTBI

i. Comparison of Neuropsychological Methods

ii. Comparison of Clinical Modalities

iii. Comparison between neuropsychological methods and clinical modalities

iv. Final comparison

6. Post Traumatic Brain Injury Care

i. Follow Up

ii. Post concussive syndrome

iii. Treatment

iv. Rehabilitation

Conclusion/Suggestion for further work

Reference

Introduction

Human nervous system is an integral system of the body which controls and monitor regulatory, creative and executive function. It is divided into two parts: central nervous system (CNS) and peripheral nervous system (PNS). CNS consists of the Brain and the Spinal cord, whereas the peripheral nervous system consists of nerves and skeletal muscles. Brain is protected by bone of the skull and structures such as meninges (three thin membranes), cerebrospinal fluid (CSF), blood brain barrier (BBB), calvaria and cerebral immune system [1].

Mild traumatic brain injury (mTBI) [4] or concussion is a neurophysiological dysfunction caused by rapid acceleration or deceleration trauma to the head. The exerted force to the head causes the brain to strike against the inner surface of the skull and rebound against the opposite side. mTBI causes neuropathological changes in the brain however, clinical symptoms are depended more on functional disturbance than structural. The cerebral blood flow is affected and decreased immediately after both TBI and mTBI. Depending on the severity, they can stay reduced for a long period. This reduced blood flow prevents oxygen and glucose supply to the tissue leading to depressed metabolism. They can also cause structural injuries such as diffuse vascular injury, brain swelling and axonal injury. Mild TBI symptoms are not easily diagnosed as the symptoms are very mild and hard to detect. Therefore, it is important to introduce a modality which will diagnose mTBI to prevent post-concussive symptoms and second impact syndrome.

Most people experience loss of consciousness immediately after a concussion. However, there are many other symptoms occurred because of concussion and they could interrelate. Each symptom varies between different individuals and they could also experience post concussive syndrome. Early or immediate diagnosis or treatment prevent or reduce persistent symptoms after mild TBI. There are two forms of tests that are carried out to detect concussion: Neuropsychological test and clinical modalities tests.  Glasgow coma scale (GCS) [5,4] test is a neuropsychological test conducted by the emergency services or at the hospital as an immediate form of treatment. a score is provided at the end of the test between 1-15 with less than 9 being severe cases. However, if the injury is severe then GCS cannot be used as the reliable source. Therefore, further testing or imaging must be conducted to further analyse the injury.

Most commonly performed test in hospitals are Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), which provide detailed, high quality images of the brain to analyse any damages to the blood vessels or part of the brain. MRI is a non-invasive imaging technique used to produce internal details of the human body and can be used in mTBI to identify acute haemorrhagic pathology. MRI can produce high resolution soft tissue images which can be crucial in the detection of mTBI. However, it has the disadvantage of not being readily available, costly equipment and procedure and increased time of procedure.

Computed tomography (CT) is an imaging technique that produces cross-sectional images representing the x-ray attenuation properties of the body. [12] The requirement [20] to perform immediate CT is if presented with following symptoms such as evident skull fracture, abnormal results from neurological examination, seizure, persistent vomiting, GCS score of less than 15. CT scan is performed to identify intracranial lesions that would require surgical intervention, follow up treatment or hospitalization. However, this occurs mainly in TBI than mTBI and therefore only fewer than 10% of cases in mTBI would present any abnormal CT results. Therefore, there is debate still undergoing whether CT is required for the identification of the presence of mTBI. CT also has the disadvantage of using ionising radiation and high costly procedure.

There are several modalities that is still under research that could potentially be used in the future as diagnostic tools for concussion. Some of those modalities are counterparts of MRI such as susceptibility weighted imaging, diffusion weighed imaging, diffusion tensor imaging, magnetic resonance spectroscopy and functional MRI. Other modalities include electroencephalography (EEG), Near infrared spectroscopy (NIRS), Ultrasound, Biomarkers and nuclear medicine (SPECT and PET). Basic function and their role in the detection of mTBI will be discussed in detail.

1.   The Brain

i.            Structure and Function of Brain

Human nervous system is one of the main systems of a body by controlling and monitoring regulatory, creative and executive function. It is divided into two parts: central nervous system (CNS) and peripheral nervous system (PNS). CNS consists of the Brain and the Spinal cord, whereas the peripheral nervous system consists of nerves and skeletal muscles. The integrated mass of CNS is made of two hemispheres, with areas containing white matter and grey matter. Grey matter (cortex and basal ganglia) consists of cell bodies of neurons while the white matter (white matter and corpus callosum) consists of myelinated and unmyelinated axons which are extension of neurons. Hippocampus and rhinencephalon contain both white and grey matter [1].

An adult brain weights approximately 1.5Kg and is composed of around 100 billion neurons. Neurons communicate with other through synapses, which gaps between each neuron. Neurotransmitters, which are chemicals that released into the synapses transmit nerve impulses across synapse [2]. Brain is divided into three parts: cerebrum, cerebellum and brain stem.

Cerebrum is largest portion of the brain which control most sensory and motor activities such as reasoning, memory, intelligence and emotional functions. Cerebrum receives its blood supply from the heart via aorta, carotid arteries and vertebral arteries. Cerebrum consist of five paired lobes which are Frontal, Parietal, Temporal, Occipital and Insular. Functions of each lobes are as follows: [2]

Lobes Functions
Frontal Control of skeletal muscles, intellectual process and verbal communication
Parietal Sensation, understanding and speech
Temporal Auditory and visual memory
Occipital Movements for focusing in eye, visual experience and other visual stimuli
Insular Memory

Table 1: Lobes inside the brain and functions of each

Cerebellum (at the back of the brain) controls balance, complex actions such as walking and talking. Brain stem connects the brain with the spinal cord and control some functions such as body temperature, blood pressure and breathing [3].

Fig 1: Anatomy of brain [2]

Brain is protected by bone of the skull and structures such as meninges (three thin membranes), cerebrospinal fluid (CSF), blood brain barrier (BBB), calvaria and cerebral immune system [1]. CSF is a clear, lymph-like fluid which forms a cushion around and within the CNS. It is formed by active transport of substances from the blood plasma in the choroid plexuses. CSF bring nutrients from the blood to the brain and removes waste products from the brain. BBB is a semi permeable membrane which protects the brain by preventing substance from entering the brain. Their main functions include preventing foreign substance form the blood entering the brain, protects the brain from hormones and neurotransmitter, and maintaining a constant temperature inside the brain. This barrier can be reduced by certain factors such as high blood pressure, traumatic injury, radiation and infection. Spinal nerve connects with the nerves in most part of the body allowing the impulses to be carried throughout the body carrying out body function [3].

2.   Mild Traumatic Brain Injury (Concussion)

i.            Pathophysiology of Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) [4] or concussion is a neurophysiological dysfunction caused by rapid acceleration or deceleration trauma to the head. The exerted force to the head causes the brain to strike the inner surface of the skull and rebound against the opposite side. Traumatic brain injury can be classified into three categories in terms of severity, such as mild, moderate and severe categories. In severe cases as the brain rebounds, it twists leading to more permanent damages.

Traumatic brain injury [6] is one of the major causes of death or disability. In USA, around 1.7b million people are diagnosed with a TBI each year, of that 52000 people die and 275000 are hospitalized. People who are at greater risk of getting a concussion is children under 4, 15-19 and above 65. The rate of recovery is higher in mTBI than in moderate and severe TBI, however patients might have disabilities that prevents them from going to school, work, and family responsibilities. The symptoms of mild TBI makes a complete recovery and it is difficult to predict the patient with Mild TBI, who could suffer from persistent symptoms and cognitive and neurophysiological deficits. Therefore, mild TBI is understudied when compared to other TBI. Symptoms of mild TBI are non-specific and could overlap with others disorders such as behavioural, developmental, mood, thought and dementia. Symptoms of mild TBI could occur weeks or months after the injury, which makes it difficult to find out whether the patient has been concussed or not.

After the rapid acceleration or deceleration, there is an unexpected release of neurotransmitter into the brain causing depolarisation. Depolarisation is the change in cell membrane polarisation due to opening of voltage gated sodium channels, causing the sodium ions to enter the nerve cell in response to a stimulus. After a depolarisation, sodium and potassium ions move into and out of the cell respectively to maintain a resting potential. Opening and closing of voltage gated sodium and potassium channels requires a high amount ATP due to active transport. The acceleration or deceleration also reduce the blood flow to the brain, and blood carries the required glucose for ATP. This reduction in blood flow cause the brain to lack energy which leads to it not functioning properly. In addition to the reduced blood flow, depressed metabolism occurs.

Regulatory [35] control of cerebral blood flow is essential because ischaemia (shortness of blood supply to tissues leading to oxygen and glucose deprivation) for minimum 4-5 minutes can lead to irreversible brain damage and potentially brain death. The control of blood flow is accomplished by cerebral perfusion pressure and cerebrovascular resistance. Cerebral blood flow is the ratio between cerebral perfusion pressure and cerebrovascular resistance. The cerebral blood flow is affected and decreased immediately after both TBI and mTBI. Depending on the severity, they can stay reduced for a long period. This reduced blood flow prevents oxygen and glucose supply to the tissue leading depressed metabolism.

Acute Mild TBI is divided into:

Concussion [4] is caused by rapid acceleration, deceleration and rotational forces causing the brain to stretch, deform, elongate blood vessels and decrease membrane permeability. Axons are vulnerable at mild TBI as they are long and can elongate into other cell bodies. Severity of the axonal damage is proportional to the severity of injury, with mild injuries producing microscopic effects on the brain.

Blast Injury [4]is an important form of TBI in civilian and military population, which are associated with blast exposure. It is caused by the rapid transmission of acoustic wave through the brain accompanied by blast winds. Blast winds could produce cerebral injury whereas blast waves cause little deformation of the brain. After a blast exposure, the blood vessels in the brain rapidly expand and contract several times causing diffuse or focal haemorrhage and edema. They could cause traumatic effect by immobilizing the brain. They are heterogenous and could be accompanied by other TBI such as impact injury. Common clinical symptoms experienced are irritability, distractibility, dysfunction, memory disturbance and cognitive abnormality.

ii.            Mild and Severe Traumatic Brain Injury Complications

Brain injuries [4] are divided into focal injuries (symptoms based on the anatomy of injury) and diffuse injuries (symptoms have more consistent effect).

FOCAL INJURIES Description
Skull fractures
  • Impact had high force
  • no serious harm to the brain.
Contusion
  • Occur where brain tissue contacts with irregular bony parts of the skull.
  • Damage to small blood vessels
Haemorrhage
  • Tearing of blood vessels at point of contact
  • Bleeding into subarachnoid space
DIFFUSE INJURIES Description
Diffuse vascular injury
  • Shearing of capillaries
  • Progress into secondary haemorrhage
Diffuse brain swelling
  • Secondary brain swelling from edema and vascular congestion
  • Swelling occurs around contusions and intracerebral haemorrhage
Diffuse axonal injury
  • Damage to axons
  • Transection of axon, disruption of blood vessels and glia.
  • Increased membrane permeability
Excitotoxicity and Oxidative stress
  • Abrupt release of neurotransmitters

Table 2: Types of Traumatic Brain Injury

Second impact syndrome (SIS) [4]occurs when someone suffers from mild TBI and experience second head injury before the first injury symptoms have resolved. SIS is a traumatic fatal injury due to rapid cerebral swelling. The second injury could be very minor and does not cause loss of consciousness however, due to resultant clinical deterioration severe cerebral edema, vascular engorgement and brain herniation could occur immediately after the injury. This is due to inability to control abrupt post traumatic loss of cerebral blood flow and catecholamine release which creates an increased intracranial blood volume and cerebral edema. SIS usually affects young athletes who plays football, boxing, karate, skiing and ice hockey as they are more prone to receive another injury before the initial one is cleared.

 

iii.            Symptoms of concussion

Most people experience loss of consciousness immediately after a concussion. However, there are many other symptoms occurred because of concussion and they could interrelate. Each symptom varies between different individuals and they could also experience post concussive syndrome. Symptoms of Mild TBI is divided into three clinical domains: cognitive, somatic and emotional.

Cognitive symptoms are associated with difficulty with concentration, decreased attention, inability to multitask, altered memory and slow reaction rate. They usually occur in the early periods of post injury and they might not correlate symptoms.  Cognitive symptoms usually disappear after 3 months of injury and the patient return to normal functioning. However, some studies have shown that even though the cognitive dysfunction has returned to normal, they will be vulnerable to various types of stress due to the enduring brain damage [4].

Somatic symptoms comprise of headache, dizziness, fatigue, insomnia, tinnitus and sensitive to noise or light. Headache and dizziness are one of the most commonly reported symptoms of mild TBI. The severity and period of headache depends solely on the individual as some patients have headache that disappears in a few weeks while others have it for three to six months and more. However, there are other factors that could contribute to headache such as migraines, musculoskeletal injuries and many more. Dizziness is sensed in the form of imbalance, vertigo, light-headedness which are all experienced in the early periods of mild TBI. Some patients have persisting dizziness which could go on for a prolonged period. Dizziness is caused after the injury due to disruption to peripheral and central vestibular functioning. Damage to the axon causes axonal injury could associated with the disruption of central vestibular pathways. Decreased hearing ability could also be caused by peripheral vestibular injury. Another mostly reported symptom is fatigue which could go on for about three months’ post injury and associated with olfactory, visual symptoms and photophobia [4,6].

Most [4] commonly reported emotional symptoms are depression and post-traumatic stress disorder and these occur at the acute period following mild TBI. These are caused due to neurobiological effects and psychological burden after the injury. There is overlap with depression caused by mild TBI and general depression before injury. Depression before injury is significantly related to the one after mild TBI. Some patients have persistent symptoms that exceed expected recovery period and could go for more than six to twelve months and they are referred to as miserable minority. There are factors causing persistent symptoms and affect normal functioning after mild TBI such as:

  • The depth of brain injury – increased damage will have prolonged symptoms and second impact syndrome could also lead to persistent symptoms
  • Other injuries – injuries not to the brain but other areas in the body such as neck pain, cervical injury and other cranial injuries.
  • Genetics – factors such as APO-E4 may contribute to prolonged symptoms.
  • Mental stress – levels of stress before and after the injury could lead to persistent symptoms. Increased stress levels could lead to fatigue and somatic symptoms after one year of injury.

iv.            Causes of concussion

Mild TBI is a common injury that affects people of any ages. The degree of injury is dependent on the degree of impact. Mild TBI is most common in sports with increased risk at football, rugby, boxing, ice hockey and skiing. It is also common in children and young adults at school to get injured while playing. Another cause of mild TBI is road accidents and accidents such falling, hitting or fighting.

v.            Current treatments for concussion

Early or immediate diagnosis or treatment prevent or reduce persistent symptoms after mild TBI. Treatment for mild TBI requires understanding of accurate diagnosis of brain injury, other injuries, post-injury biological and psychosocial factors and all the present symptoms. A detailed history from the patient and reports from witnesses present at the incident is required to acquire accurate diagnosis. Glasgow coma scale (GCS) [5,4] test is conducted by the emergency services or at the hospital as an immediate form of treatment. a score is provided at the end of the test between 1-15 with less than 9 being severe cases. However, if the injury is severe then GCS cannot be used as the reliable source. Therefore, further testing or imaging must be conducted to further analyse the injury. Most commonly test done in hospitals are Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), which provide detailed, high quality images of the brain to analyse any damages to the blood vessels or part of the brain. A biomarker is where a sample is taken from the injured area or peripheral fluid and biological or disease state is measured. This given an indication of any damages to the blood vessels or any cell death occurred in the site of injury [5].

3.   Neuropsychological Ways to detect mTBI

i.            What is neuropsychological testing?

Neuropsychological testing for concussion is a specialised evaluation method that provides a list of questions based on the symptomology, and work out a score which reveals the severity of injury. The acquired scores are interpreted by a psychologist or neuropsychologist, who is a professional specialised in understanding how neurological injury and illness affect the ability of an individual’s brain. This testing provides answers to several questions such as patient memory, attention, problem solving skills, reading, writing, and if they would require any special needs. It also answers questions such as, can they live themselves, go to work or school alone, manage day to day activities and drive [7]. Advantages of neuropsychological testing is objective assessment, non-invasiveness, more sensitive than neuroimaging and relevant functional areas of the brain [9].

ii.            Neuropsychological Questionnaire

There are two ways neuropsychological testing can be carried out, Paper and pencil test and computerized neuropsychological test. Paper and pencil test is where a list of questions is provided on a piece of paper, and a neuropsychologist will ask the patient all the question. At the end of questions, a score will be given which indicate the severity of acute brain injury. One of the most commonly used pen and pencil neuropsychological test is Glasgow Coma Scale (GCS) [8]. It is a quick, simple and reliable way of the method to check a patient’s conscious level after injury such as sports or car accident. The scoring is based on patient’s ability to talk, move and opening of eyes. The test must be conducted by a trained medical or non-medical staff at the site of injury and at emergency department in hospitals as a first form of assessment. GCS measure the following:

Eyes Score Verbal Score Motor Score
Spontaneous 4 Orientated 5 Obey Commands 6
To sound 3 Confused 4 Localising 5
To pressure 2 Words 3 Normal Flexion 4
None 1 Sounds 2 Abnormal flexion 3
None 1 Extension 2
None 1

Table 3: Basic properties of GCS

A score is given for eyes, verbal and motor and the given scores are added. Representation of the scores is given below:

Scores Level of injury Treatment
3-8 Severe Urgent medical attention, Imaging Required
9-12 Moderate Requires medical attention, Imaging Required
13-15 Mild CT or MRI may or may not show any damage. Recovers within few days.

Table 4: arrangement of GCS score

This technique has been used as a first form of assessment in concussion for many years and is still one of the most commonly used technique.

Computerized neuropsychological testing [10] is where a computer, tablet or any digital interface is used for the assessment and interpretation of brain function instead of a human examiner. The patients interact with a computer through alternative input devices (such as keyboard and mouse) with or without supervision from an expert. The interface will be programmed to test several aspects such as reaction time, balance and other questions in an interactive way. The [9] advantages of using computerized neuropsychological testing than normal is:

  • Large numbers of patients can be tested simultaneously and separately
  • The system is readily available when needed as it is fully programmed and ready for use.
  • Time sensitive testing such as reaction time and balance will be more accurate and precise
  • Reduced testing time due to adaptive testing protocols.
  • Reduced cost as once the system is bought, it can be used numerous times
  • Different languages could be administered
  • Can be used in areas where medical professional availability is low

Along [9] with the advantages, there are several factors that must be considered while developing a computerized neuropsychological testing device such as:

  • Device marketing and performance claims – developers of the system should mention the full data on how this system can be used for the diagnosis of concussion. The device should be made easy to use with clear readable fonts and alarms.
  • End user issue – the system should mention the target audience and the situations where system cannot be used. Some system would require the presence of medical expert and some doesn’t, therefore that should be clearly mentioned.
  • Technical issues – maintenance of hardware, software and firmware must be explained. Results must be reliable.
  • Privacy, data security, identity verification and testing environment – personal information of the patients should be protected and must be given most importance.
  • Patient issue; cultural, experimental and disability factors – test must be suitable to use for all types of background patients.
  • Use of computerized testing and reporting service – testing must be conducted to make sure the system is reliable and can be used to detect concussion.
  • Checks on validity and response of results

There are several technologies that have been already developed such as ImPACT which provides computerized testing for concussion. They have been widely used especially in sports where they will be non-medical expert trained to use the system. This can be used for quick assurance immediately after the injury, and it provides a quick and reliable result. If the system alerts as severe or moderate injury, then the patient can be taken to hospitals for further imaging and treatment.

Along with neuropsychological questionnaire there are other testing such as cognitive and motor and balance testing that can be carried out as part of the neuropsychological testing.

iii.            Cognitive testing

Mild traumatic brain injury causes axonal injury which can lead to obstruction in cognitive functioning such as concentration, memory, information processing and executive functioning. Cognitive testing is a non-invasive, quick and easy way of testing for these dysfunctions. It can be carried out through pen and paper or it can be programmed to be computerized to limit any bias in the results. The patients will be given several tasks such as recalling few numbers or words, reacting spontaneously to a visual stimulus, an object to focus on and reading and writing tasks. Despite many advantages there a few disadvantages to this technique such as the patient must be cooperative, the person conducting the test should be thoroughly trained as even a subtle change can make a lot of difference. This type of testing is mainly conducted in sports athletes where the test will be carried before each test for all the players to compare the postinjury results with. Some studies have found that cognitive testing conducted immediately after the injury have shown variations but normal CT results for patients with concussion. However, they cannot be used to predict post concussive syndrome as cognitive dysfunction resides few hours or days after injury in majority of patients.

Image result for checkerboard

Fig 2: Checker board, used for concentration in cognitive testing

iv.            Motor and Balance Testing

Mild traumatic injury to the brain can affect the neuronal pathways that contribute to imbalances as they are controlled by sensory input from the eyes, vestibular apparatus and skeletal muscle receptors. These are found in the spinal cord and brainstem which sent neuronal information from the brain via motor neuron. Any trauma to these areas of brain can disrupt their function and cause imbalances. Tests are usually carried out by asking the patients to walk in a line, being able to concentrate without feeling dizzy and following a path. These can determine if patient have any imbalances and then can be referred for further analysis.

Image result for balance test

Fig 3: Chart used to test the balance of a concussed patient [30]

4.   Clinical modalities to detect mTBI

i.            Magnetic Resonance Imaging (MRI)

MRI is a non-invasive imaging technique used to produce internal details of the human body. MRI involves two forms of energy; the first one is when the patient is within a very strong magnetic field to be aligned with body’s natural magnetic properties and the second one is where the area of body being investigated is exposed to very short radio frequency pulses. In between the radio frequency pulses, detectors receive signals from the body and are processed by computer.  The signal is produced by nuclear magnetic resonance where they are emitted by the nucleus of the hydrogen that is being targeted. Therefore, MRI provide information about the body in relation to the distribution and response of hydrogen nuclei present inside the body [11]

Conventional MRI [14] is used in severe and chronic cases of concussion however; it is also used in acute brain injuries such as mTBI to identify acute haemorrhagic pathology. T1 and T2 relaxation are tissue relaxing properties dependent on the proton orientation that contribute to the image contrast in MRI. T1 weighted imaging differentiate anatomical structures based on T1 values and T2 weighed imaging differentiate anatomical structures based on T2 values. In T1 weighed imaging tissues filled with water appear bright and tissues filled with water appear dark, hence useful in demonstrating anatomy of brain. In T2 weighed imaging compartment filled with water appear bright and fat content appear dark, hence useful for analysing pathology of the brain. The MRI scan for head injury analyses the T1-weighed and T2-weighed fast spin echo sequences, T2 weighed gradient echo sequences and fluid attenuated inversion recovery sequences (FLAIR). Axonal injuries with possibility of haemorrhage can be detected from the analyses of T2 weighed gradient echo sequence. Due to blood clotting in haemorrhage, hemosiderin will be deposited and this can be identified as extreme hypointense (black) region signal on MRI. FLAIR sequences are very useful in the detection of haemorrhage lesion which are not detected using T2 weighed sequences and this can be used in the detection on mTBI. On the MRI image acquired after mTBI there will be small white lesions in the lobar white matter near the junction with grey matter.

Fig 4: showing two high intensity signals after concussion in R subcortical grey matter [22]

One of the technique [14] of MRI is Susceptibility-weighed imaging which is an advanced high resolution gradient echo MRI which is very useful in detecting haemorrhages that results from DAI and deoxyhaemoglobin in venous blood. This technique can be used to detect small intracranial lesion that affects from acute injury such as mTBI. Another technique that is useful for identifying DAI lesions that are not seen on conventional MRI is Diffusion-weighed imaging. This technique focuses on Brownian motion (motion of protons in water molecules) in the extracellular space. After an injury; haemorrhage, edema or tearing of blood vessels causes the water molecules to embed from the Brownian motion. This creates a bright diffusion signal detected on diffusion weighed imaging and is extremely useful in the detection of mTBI. Diffusion-tensor imaging (DTI) is an MRI based neuroimaging technique that can identify microstructural damage. DTI can quantify and diagnose diffuse axonal injury or tearing of blood vessels to the white matter in mTBI. DTI can estimate the location and orientation which is useful in identifying abnormal directional diffusion characteristics of water molecules along axon prior to cytoskeleton damage.

Magnetic resonance spectroscopy (MRS) [14,15] is a non-invasive MRI technique with spectroscopy added to MRI to produce detailed images and measurement of chemical metabolism of brain. Metabolites such as N-acetylaspartate (NAA), choline, creatinine and lactate are released in response to neuronal injury and inflammation after traumatic brain injury. These metabolites are represented in a spectrum with peak which determines structure of the molecule by examining the position and intensities. NAA is involved in energy metabolism, and decrease in NAA levels are caused due to axonal injury. Choline is involved in membrane synthesis and increase in choline levels are due to myelin injury and cell membrane degradation. Creatinine and lactate plays a major role in cellular energy metabolism and respiration, increase in these levels are caused by damage to mitochondria or increased oxygen demand in the brain and suggests ischaemic damage. These changes are found within three days after injury and recovery seen within four weeks. Presence of these metabolites provides indication of mTBI.

Fig 5: MRS of a normal patient (left) and concussed patient (right) where the choline and NAA peaks are different [22]

Functional MRI (fMRI) [14] is a non-invasive MRI technique that produce brain activity images by detecting changes in cerebral blood flow. It is a non-radiation technique with good spatial and temporal resolution. Oxygen is delivered throughout the body by haemoglobin which is diamagnetic when oxygenated and paramagnetic when deoxygenated. This changes in magnetic property produce a change in MR signal depending on the level of oxygenation. One of the main pathophysiology of mTBI is metabolic dysfunction and cerebral blood flow changes such as increased demand for oxygen. fMRI can identify changes in cerebral blood flow by focusing on the differing properties of oxyhaemoglobin and deoxyhaemoglobin.

ii.            Computer Tomography (CT)

Computed tomography (CT) is an imaging technique that produces cross-sectional images representing the x-ray attenuation properties of the body. [12] X-rays are produced by the x-ray tube, attenuated by the patient which is then measured by an x-ray detector. Using thin x-ray beam, a set of line is scanned at area of interest, and this processes is repeated in many different angles. This allows the measurement of line attenuation for all the angles and all the distances from the centre. Using this information attenuation at each point of scanned slice can be reconstructed [12]. It is a non-invasive, ionising radiative technique that provide 3D cross sectional images of the body.

The decision to perform CT scan is made after several examinations and only those who required emergency treatment or showing severe symptoms would be transferred for a CT scan. The requirement [20] to perform immediate CT is if presented with following symptoms such as evident skull fracture, abnormal results from neurological examination, seizure, persistent vomiting, GCS score of less than 15. Patient in the following category would also be requested for a CT scan such as age higher than 60, persistent anterograde amnesia, retrograde amnesia, coagulopathy or intoxication. CT scan is performed to identify intracranial lesions that would require surgical intervention, follow up treatment or hospitalization. However, this occurs mainly in TBI than mTBI as only fewer than 10% of cases in mTBI would present any abnormal CT results. Therefore, there is debate still undergoing whether CT is required for the identification of the presence of mTBI.

CT scan is widely used for emergency treatment of mTBI as it is highly effective in detecting bleeding within and surrounding the brain and in the detection of edema. Prior to these detection, the patient might have to go through surgical intervention or follow up CT scan will be performed to monitor the progress of recovery. However, CT scan is very limited in the detection of microscopic axonal injuries and other soft tissues that could lead to long term symptoms associated with post-concussive syndrome. Modalities such as MRI is highly beneficial for the detection of soft tissue injuries. Therefore, CT is much useful for TBI than mTBI.

Fig 6: CT scan showing bifrontal mixed density subdural hematomas after severe brain injury [14]

iii.            Electroencephalogram (EEG)

Electroencephalogram (EEG) [15,16] is a device used to measure electrical signals directly from the outer surface of the brain. Using high quality and well placed surface electrodes on the scalp, patterns from the electrical activity of the brain and changes in underlying cortical electrical activity can be measured and analysed. A standard system 10-20 system is used for placing the sensors on the scalp. The most commonly used electrodes are Ag/AgCl which are disposable, high quality electrodes that obtain the signal. The acquired signals are amplified and filtered for analysis, however, in modern EEG system the signals are amplified and the converted to digital signals which are transferred to computer for further analysis and representation such as Fourier analysis. EEG provides information about spontaneous synaptic activity of neurons around the area where electrodes are placed. The acquired Biosignal is very low in amplitude and therefore must be amplified using an amplifier.

The EEG signal can be affected by alterations to structures of brain such as thalamus, brain stem or subcortical white matter. EEG is separated and grouped depending on the frequency such as alpha (frequency of 8-13cycles per second), beta (<13), theta (6-7) and delta (3-5). With a EEG acquired by placing electrodes on the scalp consists mainly of alpha and beta activity. EEG provides real time monitoring of electrical activity in the brain and it can be used in the acute period for broad assessment of cortical damage including brain death.

Quantitative EEG (QEEG) is mathematical processing of digitally recorded EEG which allows specific regions of data to be interpreted, convert the EEG into a different domain such as frequency domain and to be convert data into numerical values. This allows small changes in the electrical activity to be visualised and can be converted to many algorithms such as Fourier analyses and wavelet transform. This is useful in detecting subtle changes in cerebral electrophysiology that occurs following mTBI.

Another technique that is combined with EEG is evoked potential which provides activity of neuron in response to specific stimuli. There are several stimuli such as visual, auditory and somatosensory which are very low in amplitude than EEG signal. They should be averaged from multiple trails to distinguish evoked potential from EEG signal. Evoked potential can acquire signals from different areas of brain such as cortex, brainstem, spinal cord and peripheral nerves, whereas EEG only acquire signals within the cerebral cortex. Therefore, for the analysis of mTBI it is advisable to use evoked potential as it provides direct analysis of electrical activity in the brain stem and different pathways.

Image result for eeg sensor placement

Fig 7: showing the sensor placement for EEG

iv.            BIOMARKERS

Biomarker [13] is a naturally occurring molecule, gene or characteristic which provide an indication of medical state that can be measured accurately and reproducibly from outside the patient. One [21] of the consequences of any form of (severe, moderate or mild) TBI is diffuse axonal injury (DAI). DAI can lead to problems such as damage to axonal cytoskeleton, disruption of transport, proteolysis and swelling. This then lead ionic imbalances which leads to mitochondrial damage and reduced oxygen levels. Prior [22] to the injury to head, proteins are released due to axonal injury and neuronal supporting cells such as astrocytes will be diffused into the cerebrospinal fluid and into peripheral circulation where it can be detected. By [26] conducting a blood test, these proteins passed through blood brain barrier due to the trauma can be detected. this presence of abnormal proteins in the blood test can provide an indication whether the patients has been concussed or not. Some biomarkers that detected after injury to the head are discussed below.

S100β [20,22,27] is calcium-binding protein that is found in astrocytes which has function in controlling the intracellular calcium levels. It is found in peripheral circulation as a marker of mTBI due to damage or death to the astrocytes. Patients diagnosed with elevated levels of S100β showed symptoms of post-concussive syndrome and cognitive problems. S100β is the most extensively used biomarker as its suggested by some studies that its results correlate well the GCS score and imaging such as CT and MRI in severe TBI. Therefore, it could potentially be used as a tool to differentiate between Mild and severe TBI.

Glial Fibrillary Acid Protein (GFAP) [20]is an intermediate protein that is found in central cytoskeleton framework of astrocytes and is found only inside the CNS. Trauma [21] to the astrocytes due to head injury causes an elevation in the amount of GFAP levels which can be detected. this biomarker can be useful for the detection of several brain damages including neurodegenerative disease, stroke and mild and severe TBI. Several studies have found correlation between BFAP elevation levels and axonal injury on MRI in patients with mTBI three months after injury. Recent study found that BFAP level can be found one hour after mTBI and could differentiate concussion from other head injuries.

Ubiquitin C-Terminal Hydrolase (UCH-L1) [21]is a protein that is involved in the addition and removal of ubiquitin from proteins that are needed for metabolism. Fluctuation of metabolism occurred prior brain injury leads to an elevation of UCH-L1 concentrations. Elevation UCH-L1 was significantly higher in TBI patients and it was found using enzyme linked immunosorbent analysis. It is detected in cerebrospinal fluid and can be found from few hours to few weeks after injury therefore, early detection is possible. The levels of UCH-L1 serum was significantly higher in patients with severe TBI than mTBI and it also provides an indication of neurosurgical interferences.

Alpha-II Spectrin Breakdown Products (280 kDa) [21]is a component present in the cortical membrane cytoskeleton which is most found in axons and presynaptic terminals. Cell injury and death cause release of several cellular proteins activated by enzymes such as caspases and calpains, which have Alpha-II Spectrin as the main substrate. Elevation of Spectrin breakdown products have been found in cerebrospinal fluid after TBI. Earlier studies concluded that the Spectrin breakdown products levels are higher in severe and moderate TBI and not in mTBI. However, a recent study suggests that serum SBDP150 is significantly higher in patients with mTBI and correlates well with GCS score and intracranial injuries on CT scan.

v.            Near Infrared Spectroscopy (NIRS)

Near infrared spectroscopy (NIRS) [17] is a non-invasive technique for measuring oxygenation of tissue within the body and enables to measure oxygen saturation and other haemodynamic variables within the brain tissue. When light in visible or Ultra violet region passes through an object, it absorbs, reflect or transmit.  Visible light does not penetrate through the tissue more than 1 cm as it attenuated by absorption and scattering within the tissue. Amount of light transmitted [19] through an object is calculated using the Beer Lamberts law in relation with absorption coefficient.

I=I0e-μadwhere

μais absorption coefficient and d is optical path length (distance between source and detector). The most present molecule in the body is water and it has great absorption at wavelength greater than 900nm. Therefore, wavelength below 900nm which is in the near infrared region, photons can penetrate through deeper structures such as cerebral cortex. There are molecules such as O2Hb, HHb and CytOx present in the blood whose absorption of light varies with different wavelength and the type of molecule. Blood [18] has good absorption and scattering when presented in an optical field. Haemoglobin is the highest absorber in the near infrared region and at specific wavelength there are specific absorption and scattering coefficient for both haemoglobin and oxyhaemoglobin. Haemoglobin is a pigment that is present in the blood cells which carry oxygen from the lungs to the tissues where oxygen is used for process such as metabolism. Oxyhaemoglobin is a haemoglobin that is fully saturated with oxygen. When visible light is passed through haemoglobin, there will be colour change that takes places if oxygen is present in the haemoglobin. Therefore, oxygenated blood will produce bright red and deoxygenated blood will produce a dark red. Extinction coefficient will be different for both haemoglobin and oxyhaemoglobin at that specific wavelength.

NIRS [17] is measured by placing a light source with a specific wavelength on the forehead, light penetrates through skin, subcutaneous fat, skull, and underlying brain tissue where it is absorbed or scattered. Light is generated from a laser diode or a LED which will be placed on the forehead. A silicon detector placed few cm away from the light source measure the remitted light. Two detectors will be placed on the forehead where one measures proximal transmittance and the other measures distal transmittance. The proximal detector will detect the light that is passed largely through non-cerebral surface tissue whereas the distal detector detects light that is passed through the brain tissue. By subtracting the light transmitted from the distal with the proximal, it is supposedly used to calculate saturation from deep cerebral tissue as it is assumed that scattering is similar for both wavelength. The proximal detector will be placed around 3cm and distal detector would be around 4cm away from the light source.

Fig 8: showing positioning of head cap with sources and detectors [29]

The concentration of the molecules is likely to change during cerebral perfusion and oxygenation. The detected light would be process by a computer to digitize the data and to work out the concentration using the beer lamberts law:

A = –

ln⁡(II0) = ε(λ).c.d .

Aλ1= ελ.CHb.d+ ελ.CoxyHb.d

Aλ2= ελ.CHb.d+ ελ.CoxyHb.d

By simultaneously solving both equations with known variables it is possible to work the concentration of oxyhaemoglobin and haemoglobin. This provides an indication of cerebral blood flow and volume by using small change in oxyhaemoglobin as a tracer. This method can be used to detect mTBI as oxygen perfusion in the brain is one of diagnostic information for the detection of concussion.

Fig 9: haemoglobin signal change in contralateral motor cortex a) Concussed patient b) control [29]

vi.            NUCLEAR MEDICINE (SPECT AND PET)

Nuclear medicine involves treatment of diseases by injecting radioactivity substances inside the body and diagnosis of diseases using radioactive materials [11]. The anger scintillation camera was developed by Hal Anger, which is a 2D planar detector that produces a 2D projection image without scanning. This can be used for tomography where the projection images could be used to process the spatial distribution of the radionuclide within a slice and the image reconstruction could be applied. It was later found out that two scintillation cameras could be combined to detect the photon pairs emitting after positron emission. This process is known as positron emission tomography (PET). [12]

SPECT [22] is an imaging modality that is used to measure the amount of blood flow to a region of investigation. It is very useful in the diagnosis of brain injuries as most injuries are associated with reduced blood to the damages area and hence is the most constructive method than CT or MRI. SPECT is a type of nuclear medicine technique and involves injection of radioactive nuclides inside the body. One of two 99-m radioactive ligands (technetium 99-m hexamethylpropylene amine oxime or technetium 99-m ethyl cysteinate diethylester) is injected intravenously into the body. These molecules enter the body and cross the blood-brain barrier, where it is accumulated. The rate of accumulation is dependent upon the rate of delivery and uptake of nutrients to the volume of brain tissue in different areas of brain. This information can be used to predict the rate of cerebral blood flow in different areas of brain. Gamma camera is rotated around the brain and it detects the photons emitted by the radioactive tracer which is used to generate the 3D image of the brain.

SPECT is used widely for concussive patients better than other modalities such as CT or MRI. In the analysis of PET scan on concussive patients, most abnormalities were found in basal ganglia, frontal lobes, temporal lobes or thalamus. Some [20] studies found SPECT to be sensitive in 61% of patients with acute mTBI. Some studies conducted found abnormal SPECT results where CT scans were found to be normal. This shows that SPECT scan (blood flow analysis) is more sensitive in the detection of cerebral abnormalities in mild, moderate and severe injuries.

PET scan is used to detect cerebral blood flow, oxygen and glucose metabolism. Under normal condition, cerebral vasculature [20] transports oxygen and glucose to the brain depending on the needs of cerebrospinal fluid. As metabolism increases, the demand for oxygen and glucose also increases and the brains functions to supply these extra needs. mTBI affects the metabolic activity of the brain and then leads Hyperglycolysis and produce changes in cerebrospinal fluid to overcome this growing demands. To perform PET scan radiolabelled naturally occurring molecules such as oxygen and glucose is injected into the body intravenously. On cite cyclotron is used radiolabel oxygen and glucose as they decay quickly once entered the body. Distribution of glucose in the body is used to reconstruct the image by detecting photon pairs after positron emission. The injected isotope must accumulate in the body for 30-60 mins before conducting the scan. The PET scan produce 3D high resolution images with deeper structures of the brain.

Several studies have conducted to detect the effect of PET scan in mild, moderate and severe TBI. It produces a clear differentiation of metabolic activity in patients with severe TBI. In [22] a study conducted with patients of all severity brain injuries concluded that mTBI cannot be separately identified. One study conducted assessed cerebrospinal fluid in patients with mTBI, it was concluded that there was no difference in CBF at rest. However, while performing some memory tasks there was an alteration and increase in CBF. No definitive conclusions cannot be drawn from these studies as they are limited by the limited patient numbers and limited comparison groups. PET scan detects alteration in metabolic rate after TBI but is not yet widely used for the detection of mTBI and further studies are required.

Fig 10: PET scan showing difference between mild injury, severe injury and normal functioning of brain. Red areas are high metabolism and blue areas are low metabolism [22]

vii.            ULTRASOUND

When an ultrasound beam is projected towards a patient body, images are acquired by the energy reflected towards the source. Ultrasound is similar to x-rays in two ways, beam of energy is projected towards a patient’s body and the acquired images depends upon the energy that is attenuated by various body tissues. [11] In a normal ultrasound, the transducer send the sound wave and receives the returning wave. The transducer would be pressed down on the area of interest in the body, this send high frequency sound waves into the body. As this sound wave returns after interacting with the body’s organs such as fluids and tissues, the sensitive microphone in the transducer detects any changes in the sounds pitch and direction. These information’s are the n processed, measured and then displayed on the monitor providing real time images. Doppler ultrasound is a special type ultrasound which measures the speed and direction of blood as they travel through the blood vessels. [23]

Mild TBI causes impairment in cerebrovascular activity which leads to variation in the cerebral blood flow as its velocity become more dependent on cerebral perfusion pressure, which would not under normal conditions. Transcranial Doppler Ultrasound is applicable to measure the speed and direction of cerebral blood flow. Several patients develop secondary neurological deterioration few weeks after the injury due to cerebral ischemia. In a study carried out by Bouzat et al. and Jaffres et al found that the use of transcranial Doppler ultrasound in emergency department was useful in determining whether secondary neurological deterioration would develop. They found that the results for patients who developed neurological deterioration was different from patients who didn’t. Therefore, it was concluded that use of ultrasound in emergency department immediately after the injury would be useful in minimising post traumatic injury trauma.

 

5.   Comparison of Techniques that detect mTBI

i.            Comparison of Neuropsychological Methods

Neuropsychological tests [28] carried out post Mild Traumatic Brain injury can be useful in diagnosis, treatment and rehabilitation (if necessary). By understanding the severity and the modality of cognitive complaints, it would be easy to predict a quick diagnosis which would then determine the further actions that must be taken. Neuropsychological assessment is a standard technique that is carried out worldwide as a first form of assessment after TBI. This type of testing determines whether it is mild, moderate or severe brain injury. One of the main application and research of neuropsychological testing is in sports concussion, where it has a great advantage of the test being conducted there immediately and the quick and easy diagnosis determines whether the player can continue or stop playing. Neuropsychological testing has many advantages and disadvantage for the detect of detection of concussion. Some of them are discussed in the table below:

Advantages Disadvantages
Questionnaire
  • Quick, simple and reliable
  • Multiple tests can be carried out in short time
  • Cheap
  • Medical expertise is not required
  • In sports, if results are negative player can immediately get back into game
  • First form of diagnosis
  • Computerized questionnaires are more reliable
  • Factors affecting results:
    • Other psychological factors
    • Genetic factors
    • History
    • Testing situations
    • Fatigue
  • No anatomical information acquired [25]
  • Answers could be biased – patient lying
Cognitive Testing
  • Specific area of injury can be determined
  • Quick and simple
  • Not analysing all the areas of injury
  • Patient lying
  • Many factors affect results
Motor and Balance Testing
  • Specific area of injury can be determined
  • Quick and simple
  • Not analysing all the areas of injury
  • Patient lying
  • Many factors affect results

Table 5: Advantages and disadvantages of neuropsychological testing

ii.            Comparison of Clinical Modalities

A concussed individual with traumatic symptoms or post concussive symptoms would be taken to the hospital for further diagnosis. MRI, PET, SPECT and CT scans are the standard methods that are conducted in a hospital widely for further investigation. However, there are other modalities that could provide better future diagnosis and several advantages over MRI and CT. Modality such as EEG and NIRS would be useful to be used in sports concussion and emergency departments, as it is a portable, quick and easy machine that could provide immediate results. Biomarkers are another useful discovery which allows investigation through just a blood test. Ultrasound is another method that is found useful in the early detection of concussion and would be useful to be used in the emergency departments. Some of these modalities are still going through research and further research and testing is required before it can become a commercial equipment. There are several advantages for each of these modalities over each other, however, it is important to understand the limitation of these techniques. Therefore, it is essential to choose a method that wold provide results with less patient discomfort, less ionisation, reliable and accurate results. Some of the advantages and disadvantages of all the modalities are given below:

  Advantages Disadvantages
MRI
  • Best resolution when compared with any other modality
  • Best for soft tissue diagnosis
  • Safe – no ionising radiation exposure
  • 3D image can be acquired
  • Good to detect cerebral blood flow variations as MRI detects blood circulation and blood vessels
  • Different modes with different useful feature. E.g. fMRI detects cerebral blood flow where conventional produce structural images
  • Multiple planes of images are acquired – axial, coronal and sagittal
  • No bone artefact
  • High contrast between white and grey matter
  • Non-invasive
  • Very high costly equipment
  • Very time consuming
  • Could cause claustrophobia
  • Loud noise while conducting the procedure
  • Used more widely for post-concussive detection than emergency
  • Patients with implants cannot go through MRI procedure E.g. pacemaker, hip replacement etc.
  • Patient must be highly co-operative
  • Procedure is expensive
  • Not immediately accessible
CT
  • High resolution images are acquired
  • 3D image
  • Non-invasive – Comfortable for patient
  • Structural damages can be clearly identified
  • Detects intracranial bleeding – to determine whether surgery is needed
  • Good to traumatic brain injury(TBI)
  • Very costly equipment
  • Procedure is costly
  • Time consuming for set up
  • High radiation dose delivered to the patient
  • Soft tissue detection is not possible
  • Not applicable for mild traumatic brain injury.
PET
  • Monitor metabolism
  • Capture body function and body composition
  • Functional information is acquired such as blood flow – possible to detect changes before anatomy becomes apparent
  • Whole body scanning is possible
  • Less artefacts
  • High resolution than SPECT
  • Deeper brain structure is acquired when compared to SPECT
  • High spatial resolution
  • High costly equipment and procedure
  • Poor resolution when compared to other modalities
  • Invasive
  • Very short half-life – less imaging time
  • Half-life is crucial-must not stay in the body for longer than needed
  • Radioactive nuclide is injected intravenously – allergy
  • Ionising radiation exposure
  • Disposal of radioactive waste is complicated
SPECT
  • Functional information is acquired such as blood flow – possible to detect changes before anatomy becomes apparent
  • Cheaper than PET
  • Whole body scanning is possible
  • More widely available and used than PET
  • More half-life than PET -more imaging time
  • Metabolism is not observed like PET
  • Long scan time
  • Poor resolution
  • Invasive
  • Quantifiable estimate of blood flow is not acquired like PET
  • Injection of radioactive nuclide – allergy
  • Ionising radiation
  • Half-life is crucial-must not stay in the body for longer than needed
  •  Relied of radiopharmaceuticals
  • Disposal of radioactive waste
EEG
  • Quick / Fast procedure
  • Real time monitoring of brain activity is possible
  • Non-invasive
  • Safe – no radiation exposure
  • Low cost
  • High temporal resolution
  • Electrical activity of neuron is obtained
  • Easy to use
  • Portable machine
  • Less subject to motion artefact
  • Only used for brain activities
  • Poor spatial resolution
  • High noise signal
  • Difficult to distinguish between which part of the brain is the signal coming from
  • Electrodes must be attached for a long period – uncomfortable
  • Electrodes must be firmly placed on the scalp – hair obstruction
NIRS
  • Cheap
  • Portable
  • Non-invasive – Safe
  • Light source – no radiation
  • Natural settings
  • High temporal resolution
  • Less sensitive to head motion
  • Less environment noise
  • Real time recording
  • Quantitative measurement of changes in oxyhaemoglobin and deoxyhaemoglobin
  • Low spatial resolution
  • Can only record data from brain structure – not from inner surface
  • Depth sensitivity
  • Hair should not block light source
  • Light source and detectors must be closed off – no external light should enter
  • Probe should be secured on head to prevent it from moving – distance between source and detector must not change
  • Cannot detect any structural damage to the brain – only functional data is obtained
Biomarkers
  • Identify neurological disease at an early stage
  • Increased validity, reduced bias
  • Quick and simple
  • Low cost
  • Well correlated with clinical outcomes of mTBI
  • Risk associated with collection of fluid
Ultrasound
  • Non – ionising radiation used – safe
  • Cost effective
  • Non-invasive
  • Real time images are acquired
  • Visualise soft tissue and blood velocity
  • Quick procedure – not time consuming
  • Portable and flexible equipment
  • Speed and direction of cerebral blood flow can be detected
  • Good for detection of future post concussive symptoms of mTBI
  • Does not penetrate bone and air
  • High image noise
  • Low spatial resolution
  • Operator dependence is required
  • Structural information is not acquired

Table 6: advantages and disadvantages of all clinical modalities

Properties MRI CT N.M NIRS EEG Biomarkers Ultrasound
Physics Uses magnetic properties and radio frequency Uses X-ray radiation Gamma rays and Positron pairs Uses optical light Uses current and voltage Use protein and components in the blood Uses sound waves
Resolution High High Low Moderate Low Moderate Low
Cost of procedure High High High Moderate Low Low Moderate
Cost of equipment Very expensive Expensive Expensive Moderate Moderate Low Moderate
Real Time Analysis No No No Yes Yes No Yes
Risk/safety Safe High dose ionising radiation – not safe High dose ionising radiation – not safe Safe Safe Safe Safe
Detection of concussion Very good – high resolution soft tissue images – able to detect tiny changes to axonal injuries and other injuries to the brain Good for traumatic brain injury as high resolution structural images are obtained Very good for the analysis of metabolism and blood flow obstruction occurred due to concussion Very good for the detection of changes in oxy and deoxy haemoglobin levels after concussion Good for the analysis of electrical activity that can be impaired after concussion. Very good for the detection of proteins that pass through the blood-brain barrier after concussion Good for the monitoring of blood flow and velocity after injury.
Contrast High Moderate Low Moderate Moderate Moderate Low
Structural / functional Structural Structural Functional Functional Structural Functional Functional
Time for procedure 45 minutes 30 minutes 3-4 hours 15 minutes 15-30 minutes 15 minutes 30 minutes
Invasive / non-invasive Non-invasive Non-invasive Invasive Non-invasive Non-invasive Invasive Non-invasive
    Planar/Tomographic Tomographic Tomographic Tomographic Planar Planar Planar Tomographic

Table 7: comparison of clinical modalities

iii.            Comparison between neuropsychological methods and clinical modalities

The question whether all the concussed individuals with mild, moderate, severe injury should be taken to hospital remains unanswered. The choice between neuropsychological and clinical modalities is crucial and the importance of one over the other must be known. To understand whether both the tests or just one is sufficient to detect concussion, it is important to know the advantages and disadvantages of them each. Some of the advantages and disadvantages are given below:

  Advantages Disadvantages
Neuropsychological
  • Quick and easy
  • Assessment is based on symptoms present
  • Beneficial for rehabilitation as routine tests can be conducted to track the progress and control post traumatic symptoms
  • Does not require a medical expertise to conduct the test – anyone who is trained can conduct the test. E.g. sports coach
  • No physical harm done to the patient
  • Results are not always reliable – patient lying, biases answers
  • Difficult to understand the category of symptoms e.g. rating the headache
  • No structural or functional information is obtained – cannot understand the exact injury inside the brain
  • No physical images or data can be acquired
  • Could be mentally exhausting for a person who just got concussed
Clinical Modalities
  • Structural and functional images are acquired – exact diagnosis
  • Standard treatment for concussion – available in all hospitals
  • Helps prevent second impact syndrome
  • Can determine whether surgical intervention is required
  • Relieves symptoms quickly as diagnosis is promising and treatment is conducted immediately
  • Results are always reliable
  • Patient discomfort
  • Trauma and discomfort to patient
  • Radiation exposure is possible
  • Expensive
  • Hospital visit is required
  • Medical expertise must be present

Table 8: Comparison of neuropsychological methods and clinical modalities

iv.            Final comparison

Neuropsychological testing can only be used a first form of assessment in mild, and moderate cases. It cannot be used as a diagnostic modality as its results are not 100% reliable. Therefore, for severe cases of TBI the patient must be taken into hospital for further investigation through CT and MRI. However, [31] they have limitations in assessing diffuse axonal injury and metabolic activity due to microscopic lesion and cerebral physiology. They also have disadvantages such as radiation, non-availability and high cost. Therefore, other modality such as NIRS, ultrasound, EEG and biomarkers can be used in the beginning. From the results achieved severe cases can be transferred for a CT or MRI for further analysis. But for mild and moderate cases of TBI, NIRS, EEG, biomarkers or ultrasound can be used. These all have an advantage of no radiation, low cost and good correlation with outcome of mTBI. Therefore, these techniques can be immediately performed in the emergency department and conclusion can be drawn from the results. Depending on the severity, they can be either send home or stayed in the hospital for observation. Severe cases can be transferred for further investigation or surgical intervention.

6.   Post Traumatic Brain Injury Care

i.            Follow Up

A patient seeking medical attention in hospital after concussion will follow through the follow chart that is given below. Severe cases will go through surgical intervention and moderate and mild could be given drugs to control and reduce the systems. If there are any post traumatic symptoms few weeks later the incident, then MRI or CT will be conducted and will be send to rehabilitation for safe and speedy recovery.

Fig 11: flow chart of follow up scheme of mild TBI. LOC is loss of consciousness, PTA is post traumatic amnesia and NPO is neuropsychological assessment. [6]

ii.            Post concussive syndrome

Patients [32] with mTBI will recover within 7-10 days’ period, however children’s and adolescence take a while longer than adults. The exact recovery time cannot be determined as it is based on age, sex and history of prior concussion. The presence of symptoms beyond generally accepted time can lead to post concussive syndrome (PCS). In sports-related concussion, normal recovery is within 2 weeks and non-sports related recovery is within 3 weeks.

PCS [32,33] is the continuous occurrence of three of the following symptoms such as headache, dizziness, fatigue, irritability, insomnia, concentration difficulty or memory difficulty. Most patients present with insecurity of symptoms after mTBI and the challenge is to determine whether the symptoms are based on concussion pathophysiology or clinical depressive symptoms. If the symptoms present is getting worse with excursion but getting better with rest, then it is less likely to be concussion pathophysiology. However, if the symptoms persist even at rest it could be related to prolonged inactivity or from mental depression about inability to return to normal life routine. Therefore, it is essential to understand that the symptoms reoccurring is concussion based. To return into normal life routine, prescription might be given to reduce the symptoms or will be send to rehabilitation to diagnose and treat the symptoms.

iii.            Treatment

Medication [4] in the form if drugs are usually given to a concussive individual to reduce the symptoms of agitation and depression that occurs because of recovery from a minimally conscious state or if there persisting symptoms such as amnesia and headache. These agitations can least from days to months after injury. The initial treatment for agitation if providing a friendly and safe environment for both the patient and caregiver. Some medication that manage aggression can alter the recovery of the brain. However, if agitation is progressive then drugs such as β-blockers, neuroleptics, antiepileptics and neurostimulants are given to reduce them symptoms.

To control [34] other symptoms drugs such as diuretics which will reduce the pressure inside the brain will be given. If seizure was present after injury, anti-seizure drugs will be given to reduce additional damages to the brain. Rarely coma-inducing drugs are given to place the patient in a temporary coma as comatose brain require less oxygen to function. This is only done if the blood vessels are severely compressed by increased pressure leading to inability to deliver oxygen and nutrients to brain cells.

Surgery [34] is conducted in severe cases to reduce additional damages to brain cells and tissue. One of the surgeries conducted is removing hematomas which are blood clots that are formed which will insert more pressure on the brain tissue. Repairing skull fractures must be performed if the skull is broken or damages severely.  Another surgery is opening a window in the skull where pressure is relieved by draining the accumulation of cerebrospinal fluid or surface area for swollen tissues by creating a window.

iv.            Rehabilitation

Patients with severe traumatic brain injury would require rehabilitation to improve their abilities to perform daily activities. The time and type of rehabilitation is completely dependent on the patient and the type of injury. Specialist rehabilitation departments include psychiatrist, occupational therapist, physical therapist, speech and language therapist, neuropsychologist or councillor. Rehabilitation areas include problem-solving training, attention, working memory, long term memory, moving and walking. There will be tasks and activities involved with all the rehabilitation areas and that would require the patient to stimulate affected area of the brain. This would enhance the treatment for post traumatic symptoms and also would allow the patient to return to normal daily activities.

 

 

 

 

 

 

 

 

 

 

Conclusion/Suggestion for further work

Mild TBI is a common brain injury that affects thousands of people, mainly in sports every year. Pathophysiology of concussion is mainly functional changes in the brain than structural. Therefore, symptoms are varied between individual and the occurrence of symptoms are also varied. In some patients, the symptoms appear immediately after injury, however other patients have symptoms occurring or reoccurring weeks or months after injury. There are several cases where GCS were performed immediately after the injury and the results showed negative stating the patients wasn’t concussed when they were concussed. CT scan performed in hospital also produced negative results when it was positive. This clearly states that mTBI injuries can be very mild that the detection of injury is very difficult.

GCS is the gold standard technique that is performed immediately after any type of brain injury to understand the neurological changes. GCS calculated scores can determine whether the patient injury is mild, moderate or severe. However, GCS can only be used immediate source detection as further diagnosis is required to understand the type of injury inside the brain. Therefore, severe cases and high GCS scored patients will be taken into hospital for further diagnosis. CT is the standard diagnostic imaging modality that is performed to detect any structural changes inside or outside the brain. They are extremely useful in severe TBI and cases where surgical intervention is required. However, they are not capable of providing functional and soft tissue injuries that is mostly found in mTBI. Moreover, it has other disadvantages such as high radiation and high costly procedure.

MRI is the other imaging modality performed in the hospitals for the detection of mTBI and they provide high resolution images of soft tissues and haemorrhagic pathology. However, MRI is not readily available in the hospital as it is a very costly equipment and requires long period to perform the test. There are other counterparts of MRI that can be used for the detection of concussion such MRS which detects metabolites such as acetylaspartate (NAA), choline, creatinine and lactate. These are released in response to neuronal injury and inflammation after mTBI. Functional MRI (fMRI) is another technique that produce brain activity images by detecting changes in cerebral blood flow and can indicate depressed metabolism and changes in cerebral blood flow after mTBI.

EEG can measure electrical activity of the brain by placing electrodes on the scalp and measure the variations in neuronal activity after mTBI. This is quick and easy method; however, it has high noises interrupting the signal making it harder to analyse. Biomarkers measure protein molecules such as S100β, Glial Fibrillary Acid Protein (GFAP), Ubiquitin C-Terminal Hydrolase (UCH-L1) and Alpha-II Spectrin Breakdown Products (280 kDa) which pass through blood – brain barrier because of mTBI. These can be detected through a blood test.

Nuclear medicine involves treatment of diseases by injecting radioactivity substances inside the body and diagnosis of diseases using radioactive materials. SPECT is an imaging modality that is used to measure the amount of blood flow and is very useful in the diagnosis of brain injuries as most injuries are associated with reduced blood to the damages area. PET scan can be used to detect cerebral blood flow, oxygen and glucose metabolism which also can be used for the diagnosis of mTBI. However, they have the disadvantage of injecting ionising radiation into the body and very low resolution images acquired.

All these modalities are still going through further research and could be used as a diagnostic tool for the detection of concussion in the future. Ultrasound, EEG and NIRS are quick, easy and less costly than all the other modalities. They have the capability to detect mTBI and can be used as an emergency technique for immediate diagnosis and treatment. However, further research is required to understand the reliability of results with mTBI. Patients with severe cases of TBI can be then referred for further diagnosis by modalities such as CT, MRI, SPECT or PET. There is still several research being carried out to find what exactly happens inside the brain during mTBI therefore a better diagnosis can be discovered and the chances of second impact syndrome can be reduced.

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