Lecture 7: mTBI Flashcards
What are concussions?
- can also be referred to as mild traumatic brain injuries (mTBI)
- Defined as a biomechanically induced transient disturbance of neurological function; biomechanical means the brain is physically moving which causes/induces a transient (which means comes and goes) symptoms. This is the difference between a mild traumatic brain injury and a traumatic brain injury
- not every concussion is the same -the symptoms can vary widely because it all depends on where the brain got damaged
What can concussions cause?
- May or may not be associated with loss of consciousness (LOC);
- Temporary loss of brain function;
- Produce a variety of physical, cognitive and emotional symptoms (often subtle);
- Symptoms subside naturally.
What is the difference between a mTBI and TBI?
if we have to do anything to get rid of the symptoms, then it’s a traumatic brain injury but if we don’t have to do anything to get rid of the symptoms then it’s a mild traumatic brain injury (concussion). Also if the symptoms are transient`
What causes a concussion?
- Rapid acceleration and/or deceleration of the brain.
- Resulting in brain colliding with skull, both the front and back (or side to side)
- Coupe-Contre Coup (brain hits front of skull and then back; two points of damage) -dual point of impact
- Brain contusion and cerebral edema may persist for 48 hours
- Increased intracranial pressure; because there’s two points of impact, there’s pressure on both sides of the brain which can increase the intra-cranial pressure
- Impact can be direct or indirect (ex. sound), it doesn’t matter (sport related collision vs. blast exposure at war).
- Impact can be linear, rotational or angular (or, probably, a combination of all), this DOES matter.
- Direction of force is extremely important for predicting extent of injury/recovery
- —> linear (front/back) impacts are the safest rather than rotational (brain is rotating) which are more dangerous
- -Direction of force makes it difficult to compare concussions between patients (in humans) because you never know where the impact came from/how you got injured
What do rotational forces cause?
- diffuse axonal injury: shearing forces cause axons to detach from cell body;
- Damaged axons display indiscriminate release of the excitatory neurotransmitter glutamate;
- Excitotoxic (too much excitation) lesions subsequently occur from 24-48 hours post injury
- leads to subdural and epidural hematoma –> a collection of clotted blood and accompanying increased pressure on the brain.
- Brain contusions (bruise) are typically viewed as the hallmark of brain damage following a brain injury.
- can lead to neural & vascular tissue damage
What dictates concussion severity?
- The magnitude of rotational force
- Parts of the brain most affected by rotational forces are the midbrain and diencephalon (in the brain, there are clusters of grey matter and clusters of white matter, which have different densities. So different densities will move at different rates when physically impacted)
- -Also damages frontal and temporal lobes.
What causes the loss of consciousness in concussions?
Disruption of normal cellular activities in parts of the midbrain and diencephalon is thought to produce LOC (loss of consciousness)
What is glutamate?
- Glutamate is the main excitatory neurotransmitter in the brain (It is present in more synapses than any other neurotransmitter and GABA is the second most common)
- Once released into the synaptic cleft, glutamate can bind to three post-synaptic receptors:
1) AMPA receptors;
2) NMDA receptors;
3) Kainate receptors.
- Once released into the synaptic cleft, glutamate can bind to three post-synaptic receptors:
- All 3 receptors allow Na+ entry into the post-synaptic cell and therefore cause depolarization and excitatory post-synaptic potentials.
- NMDA receptors are permeable to calcium.
- too much calcium inside the cell can signal for apoptosis (Calcium is good and needed but at moderate levels, too much coming in signals to the neuron that something is wrong so the cell self-destructs)
How is the over-excitation of glutamate harmful as seen in concussions?
- Too much glutamate being released can cause damage to surrounding neurons.
- Excitotoxicity can occur with overexposure to glutamate (or other excitatory AA’s), caused by a prolonged depolarization of the postsynaptic neuron.
- When neurons are subjected to prolonged stimulation by glutamate, a large % of cells die via 1 of 2 mechanisms:
1. Necrosis: characterized by rapid lysis of the cell due to osmotic swelling; the cell takes in a lot of water to dilute the concentration of all the ions that have flood in due to prolonged excitation of the neuron
2. Apoptosis: delayed cascade of biochemical events that leads to DNA breakup and ultimately cell death. The neurons self-destruct in a very organized and efficient manner, in which the parts then get recycled to neighbouring neurons, unlike necrosis
- When neurons are subjected to prolonged stimulation by glutamate, a large % of cells die via 1 of 2 mechanisms:
- -> Glutamate activation of NMDA receptors can allow the entry of calcium (Ca2+) into the cell.
- -> Ca2+ is sequestered in mitochondria and interrupts normal function; the mitochondria acts like a sponge and absorbs all the excess calcium
- -> ATP production is hindered;
- -> Can lead to initiation of apoptosis.
- Na-K pumps are working in overdrive to restore ionic homeostasis (bring out 2 sodiums and bring in 3 potassiums) and this requires a ton of ATP because it is going against the concentration gradient
- However, increased demand for glucose comes at a time when the mitochondria are not functioning to provide ATP (because of too much calcium absorbed) so these pumps can’t use energy. We need oxygen to generate ATP (oxygen is required to metabolize glucose into ATP). The blood delivers oxygen but it can’t properly because if the hematoma
- -Hypoglycemia ensues, leading to cognitive deficits and an energy crisis that leads to secondary injuries.
What are the secondary injuries in concussions as a result of the over-excitation of glutamate?
- Anaerobic glucose metabolism (glycolysis) involves production of lactate –> lactic acid
- Overproduction of lactic acid results in acidosis, and subsequent damage to the blood brain barrier (BBB).
- BBB permeability follows, leaving organism extremely vulnerable to outside toxins.
- -Secondary effects may take days, weeks or months to develop, and can persist for weeks, months and even years
What is second impact syndrome (SIS)?
- Occurs when an individual suffers a concussion while still symptomatic from a previous concussion;
- Prior concussions increase the likelihood of a 2nd concussion
- Repeated concussions have a cumulative effect on the human brain.
- SIS carries a 50% mortality rate, 100% morbidity rate (in animal models).
What are the clinical symptoms of mTBI?
1) Headache, pressure in the head –> vascular injuries;
2) Temporary loss of consciousness (LOC) –> brain stem;
3) Confusion –> corpus collosum; bundle of white matter which is surrounded by grey matter. this is a difference in density so it can cause the corpus callosum neurons to be left behind when the brain is accelerating causing neuronal tears.
4) Amnesia surrounding the event –> hippocampus, frontal lobes;
5) Ringing in the ears –> temporal lobes;
6) Nausea and/or vomiting –> area postrema; not protected by blood-brain barrier which makes sense because if you eat something poisonous or toxic the brain has to detect that and initiate vomiting. this area thus initiates the gag reflex. In concussions, you have an indiscriminate release of glutamate which excites these neurons in the area postrema which makes the patient feel nauseous
7) Changes in mood and emotional disturbances
- -> amygdala
What is the detection and diagnosis of mTBI?
Sport Concussion Assessment Tool – 5th Edition (SCAT-5)
– The SCAT-5 is a standardized tool for evaluating concussions;
– Designed for use by physicians;
– Pre-season SCAT-5 scores are useful for comparing pre/post injury results;
SCAT-5 involves:
– Checklist for observable signs of trauma;
– Memory assessment;
– Glasgow Coma Scale (GCS) assessment; tests level of consciousness
– Symptom inventory (completed by athlete);
– Battery of cognitive screening tests;
– Neurological screen
If you are not a medical professional, the Concussion Recognition Tool 5th edition is recommended or the Immediate Post Concussion & Cognitive Testing (ImPACT).
- -Computer-based battery of tests aimed at detecting post-concussive symptoms;
- -Demographic questionnaire;
- -Symptom Inventory;
- -Injury Evaluation;
- -20-minute neurocognitive test.
What is chronic traumatic encephalopathy?
- Chronic Traumatic Encephalopathy (CTE, aka dementia pugilistica) is the result of multiple, sub-concussive blows to the head.
- This is not a concussion issue.
- CTE is a progressive degenerative disease found in individuals with repeated head trauma (e.g. boxers, football players, hockey players, etc.).
- Characterized by neurofibrillary tangles, plaques and neuronal death.
