Module 2 - Stroke and TBI Flashcards
Why are midline structures more susceptible to trauma?
Held rigidly in place by dura and at the centre resulting in shearing or tearing force generated by rotational trauma as the two hemispheres shift move separately to one another.
Describe what effect raised intracranial pressure has had on the brain.
Midline deviation, ridge on the uncus of the right temporal lobe indicates it’s herniated through the tentorial notch. Also the top of the right cerebellum has been squashed by the herniated lobe.
What can be seen on histology of diffuse axonal injury?
Axonal swellings, retraction bulbs?
Where is DAI most likely to be seen?
Parasagittal parts of the brain, the corpus callosum, fornix, internal capsule, and the brain stem.
What happens in transtentorial or uncinate herniation?
The medial aspect of the temporal lobe is compressed against the free margin of the tentorium. With increasing displacement of the temporal lobe, the third cranial nerve is compromised, resulting in pupillary dilatation and impairment of ocular movements on the side of the lesion.
Where does hypertensive Intraparenchymal haemorrhage occur?
The putamen (50 to 60%) of cases, thalamus, pons, cerebellar hemispheres (rarely), and other regions of the brain.
Describe the gross pathology of traumatic brain injury:
Contusions = bruise on brain
Lacerations = break in the pia mater
Different types of herniations, haematomas, etc. Diffuse axonal injury possible too.
Describe the histology of TBI:
Blood, retraction bulbs, venous congestion, perivascular oedema, axonal changes and splitting of the ependymal layer from the rest of the grey matter.
What is a mild, moderate and severe TBI using GCS scores?
>12 = mild 9-12 = moderate <9 = severe
What are some symptoms of base of skull fractures?
Otorrhea, rhinorrhea, raccoon eyes, Battle’s sign
What midline structures are commonly affected and why?
Corpus callosum, rostral brainstem, septum pellucidum - they are held in place by the dura and then the rotational forces damage the structures as the two hemispheres move past each other.
What are the gradings of DAI?
Grade 1: Parasagittal frontal, internal capsule, cerebellum.
Grade 2: + Corpus callosum
Grade 3: + Dorsal brainstem
What is the pathogenesis of DAI?
Damage leads to calcium activated proteases such as calpain. The axon is completely severed in primary axotomy but stabilises in secondary axotomy, only to completely severe later on and produce a bulb.
What causes the raised ICP?
Vasodilatation + increased CBV (congestion) + blood vessel damage (vasogenic oedema) + increased water content of cells (cytotoxic cerebral oedema)
Role of immune system in TBI?
BBB breakdown + PMN infiltration + Macrophage/microglia activation -> ROS + oedema + cytokines + complement activation + phagocytosis -> apoptosis/necrosis/repair
Head trauma can cause a poor clinical outcome long after the immediate injury by initiating an inflammatory cascade causing damage to multiple neural cell-lines. This cascade up-regulates cytokines such as IL1ß inducing apoptosis and DNA fragmentation of oligodendrocytes and neurons via Fas ligands. This results in cell death followed by inflammation and further expansion of the initial neurological lesion of the brain parenchyma, thus worsening the resultant cognitive deficit.
Molecules such as TNFα are released after trauma and this predisposes astrocytes to apoptosis. While neural and synaptic damage from TBI creates the lesion, it is the lost trophic support from astrocyte-derived BDNF that limits regeneration/ recovery.
What is the definition of CTE?
(i) foci of perivascular NFT and astrocytic tangles
(ii) irregular cortical distribution of NFT and astrocytic tangles with a predilection for the depths of sulci
(iii) clusters of subpial and periventricular astrocytic tangles in the cerebral cortex, diencephalon, basal ganglia and brainstem
(iv) neurofibrillary tangles in the cerebral cortex located preferentially in the superficial layers.
Give some examples of primary and secondary damage in TBI:
Primary: Lacerations, fractures, contusions, haemorrhages, DAI
Secondary: Ischaemia, hypoxia, cerebral swelling, infection
What are the different types of herniation?
Subfalcine herniation of cingulate gyrus
Transtentorial/uncinate herniation of media temporal lobe
Transforaminal herniation of cerebellar tonsil
Describe the appearance of haematoma:
Extradural: dome shape
Subural: Crescent
Subarachnoid: white around edges in an MRI, lots of blood near vessels in post mortem
Describe the gross pathology of stroke:
Haemorrhage within the parenchyma.
Describe the histology of stroke:
Red neurons, neutrophil infiltration, macrophages, loss of myelin, gliosis.
Define a stroke:
Acute-onset neurological symptoms or signs indicative of focal central nervous system dysfunction, due to vascular cause (ischemia/hemorrhage), lasting >24 hours.
2nd commonest cause of death after cancer (with heart disease)
How does head trauma lead to post-traumatic epilepsy (6% epileptics)?
TBI can cause disruption to the blood-brain-barrier(BBB), resulting in neurological complications by reducing a patient’s seizure threshold, leading to post-traumatic epilepsy. Up-regulation of cytokines such as IL6 after injury increases the permeability of the BBB by disrupting the integrity of its tight junctions, causing albumin extravasation. This alters the local ionic environment as astrocytes cannot then buffer potassium ions, which increases neuronal excitability and thus lowers the seizure threshold.
How is TBI pathology similar to AD pathology?
Reduced cognitive function also results from tau deposition after TBI. Trauma causes damage to the integral structure of microtubules resulting in peri-vascular tau deposition in brain parenchyma. Subsequent tau hyper-phosphorylation causes development of neuro-fibrillary tangles. These insoluble tangles limit axonal conduction, prevent axonal transport and eventually cause cell death. This then leads to memory and executive dysfunction which has a significant long-term impact on the patients’ ability to function, limiting their independence and quality of life. McKee 2009
The expression of the APOE gene is a genetic risk factor for deposition of Amyloid ß plaques post-TBI, and the expression of such genes confers a neurological risk factor for poor outcome after TBI. Amyloid ß deposition is a pathophysiological mechanism that contributes to symptoms of Chronic Traumatic Encephalopathy (CTE).
After TBI, axonal damage causes amyloid precursor protein to be deposited in cell bodies and axons. This then increases the local concentration of soluble amyloid ß locally through aberrant cleavage resulting in deposition of diffuse Amyloid ß plaques. It is hypothesised that this could play a role in the symptoms of disordered cognition and changes in mood and memory that patients experience in CTE. It is clear that head trauma is a key factor in the development of this syndrome; however, the APOE gene renders the individual more susceptible to this specific negative consequence of head injury, causing clinical outcome after TBI to worsen. Gavett 2010
