DIFFUSE AXONAL INJURY AND ITS MANAGEMENT.pptx

This topic discusses about Diffuse axonal injury, its types and management.
It also discusses about the radiological features and its management.

1. DIFFUSE AXONAL INJURY Dr bipul thakur 5/24/2024 1

2. HEAD INJURIES Head injury is defined as any trauma to the head other than superficial injuries to the face. Traumatic brain injury (TBI) is a nondegenerative , non congenital insult to the brain from an external mechanical force , possibly leading to permanent or temporary impairment of cognitive, physical and psychosocial functions with an associated diminished or altered state of consciousness. 5/24/2024 2

3. TYPES OF TRAUMATIC BRAIN INJURY PRIMARY BRAIN INJURY Occurs at the time of trauma Cortical contusions Lacerations Bone fragmentation Diffuse axonal injuries Brain contusions 5/24/2024 3

4. SECONDARY INJURIES: Develops subsequent to the initial injury Preventable It include injuries from the hematomas, edema, hypoxemia, ischemia (primarily due to the elevated ICP), vasospasm 5/24/2024 4

5. Grading of head injury 5/24/2024 5

6. Diffuse axonal injury A form of post traumatic brain injury which occurs over a broad swath of myelinated tracts of the CNS resulting in significant neurological events ranging from loss of consciousness to persistent vegetative state. Primarily affects white matter tracts in the brain. Occurs in the 50 % of severely head injured patients and accounts for 35% of death from head injury DAI is defined as prolonged > 6 hr loss of consciousness without visible mass or ischemia. Now a days the term TIA (Traumatic axonal injury) is used. 5/24/2024 6

7. Causes of DAI Accidental falls Vehicular accidents Child abuse Assaults Gunshots Violent shaking of child Sport related injuries 5/24/2024 7

8. Clinical grading of diffuse axonal injury Mild : coma > 6-24 hrs followed by mild to moderate memory impairment, mild to moderate disabilities Moderate : coma > 24 hrs , followed by confusions and long lasting amnesia, mild to severe memory , behavior and cognitive deficits Severe : coma lasting months with flexor and extensor posturing . Cognitive, memory, speech, sensorimotor and personality deficits. Dysautonomia may occur 5/24/2024 8

9. Adams diffuse axonal injury Grade 1 : mild axonal injuries with microscopic white matter changes in cerebral cortex, corpus callosum , brainstem and less commonly , cerebellum Grade 2 : Moderate DAI with Gross focal lesions in the corpus callosum in addition to above Grade 3 : Severe DAI with focal lesion in the dorsolateral quadrant of the rostral brainstem in addition to above 5/24/2024 9

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11.   Pathophysiology of DAI complex and lacking a unifying theory. The assumption that TAI is primarily and solely caused by direct mechanical force has been abandoned. Besides the primary damage, there is secondary damage caused by chemical alterations and changes in neuronal metabolism. 5/24/2024 11

12. Trauma mechanism Two major mechanisms involved in head trauma: direct impact accelerative and decelerative (a/d) forces. Sudden head movement produces a force vector inside the intracranial cavity resulting in shearing and strain injury. Shear and tear of axonal fibers can cause axonal damage resulting in TAI. a/d forces in the coronal plane are primarily associated with the occurrence of TAI Slower A/d forces with a relatively long duration (20– 25 ms ) will mainly cause TAI 5/24/2024 12

13.  Primary axotomy Pure mechanical stretch due to traumatic acceleration or deceleration alone Leads to direct tearing of axonal fibers. Subsequently to this tearing, the damaged axonal fibers would retract forms retraction bulbs, which are visible on pathological examination This process of direct tearing is called primary axotomy.  5/24/2024 13

14. Secondary axotomy Is an inflammatory and apoptotic event If the inertial forces are of low intensity and do not cause complete primary axotomy can still be strong enough to cause partial damage to the axon, trigger a molecular pathway resulting in secondary axotomy. 5/24/2024 14

15. Secondary axotomy is an inflammatory and apoptotic event While the primary axotomy is a true mechanical event, caused by shearing forces. Secondary axotomy can also be seen as a continuation of primary axotomy where the initial structural damage caused by the traumatic forces forms the base for the entire molecular cascade, instead of as a separate entity. 5/24/2024 15

16. Secondary axotomy 1. The microtubules (blue) become progressively stiffer and eventually break 2. leading to a disruption of the axonal transport of molecules. 3. Calcium accumulates in the cell (both through the mechanical opening of calcium channels, as well as through the disruption of mitochondria). 4. Through hydrolyzation of calpastatin (which normally inhibits calpain), calpain is activated and it in turn hydrolyzes the cytoskeleton and microtubules. 5. This cascade leads to apoptosis and axon disconnection 5/24/2024 16

17. CLINICAL FEATURES Loss of consciousness Cognitive and memory deficits Sodium and free water derangements 5/24/2024 17

18. Diagnosis: Histopathological findings Large axonal dilations caused by complete axotomy, referred to as retraction bulbs or axonal bulbs. Axonal varicosities: - are dilations along the length of the axon, visible within several hours after trauma 5/24/2024 18

19. Histopathological findings Traditionally hematoxylin and eosin (HE), and several silver stains were most widely used to detect pathological changes. immunohistochemical staining is more widely used now. Accumulation of beta-amyloid precursor protein ( β- APP) - sensitive marker for diagnosis of TAI Accumulation of β- APP is visible within 2 h after trauma and shows more extensive injury than HE or silver staining. 5/24/2024 19

20. Radiographic features typically located at the grey-white matter junction, in the corpus callosum and in more severe cases in the brainstem MRI is used for grading of TIA 5/24/2024 20

21. CT scan   Non-contrast CT  - routinely done in head injuries. Not sensitive for diffuse axonal injury The appearance depends on whether the lesions are hemorrhagic or not. Hemorrhagic lesions will be hyperdense and range in size from a few millimeters to a few centimeters in diameter Non-hemorrhagic lesions are hypodense. 5/24/2024 21

22.  deep shearing-type injury in or near the white matter of the left internal capsule (arrow). 5/24/2024 22

23. MRI Conventional MRI ( cMRI ) has a higher sensitivity in demonstrating lesions in the brainstem and the deep white matter, making it more sensitive for identifying axonal injury compared to CT The MRI gradient echo sequence (GRE) is able to detect heme and heme breakdown products making it a suitable method for discovering small hemorrhagic lesions. Diffusion weighted imaging can accurately examine non haemorrhagic lesions. High signal DWI can be used in patient with early stage TAI . Lesions found represent cellular swelling and cytoxic edema. 5/24/2024 23

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25. and (B). Axial FLAIR images showed some punctate hyperintense foci in the subcortical white matter of the right frontal lobe (arrow) and the splenium of the corpus callosum. (C) and (D). DWI and ADC maps indicated restricted diffusion within the splenium of the corpus callosum https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571536/ 5/24/2024 25

26. Susceptibility weighted imaging (SWI) as a variant sequence of GRE imaging considered the “gold standard” for identifying TAI lesions. It has a higher sensitivity for hemorrhage than GRE , more useful for early diagnosis of TAI SWI might overestimate the size of a lesion due to its high sensitivity to heme products 5/24/2024 26

27. SWI multiple hypointense foci of hemorrhagic lesions at the grey-white matter junction of bilateral temporal lobes(A), bilateral frontal lobes (B), posterior limb of the left internal capsule (C), the fornix commissure, and the splenium of the corpus callosum (D) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571536/ 5/24/2024 27

28. Diffusion tensor imaging (DTI) is an improved form of DWI. can be used to evaluate nerve alignment, white matter microstructure and the morphology around nerve fibers . Within the first 24 h after trauma, DTI can detect white matter regions with reduced anisotropy, making it an adequate technique for detecting TAI 5/24/2024 28

29.  disrupted white matter fibers in the posteroinferior aspect of the splenium (arrow, A), left crus of the fornix (arrow, B), subcortical frontal tracts (circle C and arrow D https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571536/ 5/24/2024 29

30. BIOMARKERS C tau levels in CSF NEUROFILAMENT MARKERS GLIAL FIBRILLARY ACIDIC PROTEIN MYELIN BASIC PROTEIN S-100 β NEURON-SPECIFIC ENOLASE UBIQUITIN CARBOXY-TERMINAL HYDROXYLASE L1 5/24/2024 30

31. Treatment DAI lacks a specific treatment Stabilization of the patient Limit increases in intracranial pressure (ICP). Rehabilitation - include: Speech therapy Physical therapy Occupational therapy Recreational therapy Adaptive equipment training Counseling 5/24/2024 31

32. Treatment: preventing secondary axotomy  Ca-channel blocker : nimodipine could play a role in preventing or minimizing secondary damage of the axon. Preclinical studies showed a decreased expression of β- APP, suppressed activity of calcineurin ( CaN ), and lessened ultrastructural axonal damage Paclitaxel(Taxol) has possible effect on limiting axonal degeneration 5/24/2024 32

33. Treatment: preventing secondary axotomy   Ciclosporin A ( CsA ) :Inhibits Calcineurin. By preventing a rise in mitochondrial membrane permeability CsA abates swelling and disruption of mitochondria and thereby mitigates axonal damage It also antagonizes calcium-mediated cytoskeletal disruption, and thereby secondary axotomy Others: EPO Hypothermia Progesterone Enhancing neuronal regeneration stem cell therapy 5/24/2024 33

34. Treatment is performed in conformity with the “Guidelines for the Management of Severe Traumatic Brain Injury” RECOVERY TIME OF TIA : According to the grade Grade 1: 1 week Grade 2 : 2 week Grade 3 : 2 month 5/24/2024 34

35. PREVENTION The  Centers for Disease Control and Prevention (CDC Trusted Source recommend that people reduce the risk of sustaining a TBI by : wearing a seatbelt whenever riding in or driving a vehicle avoiding driving when under the influence of drugs or alcohol wearing the appropriate protective gear or helmet for the sport or activity evaluating an older adult’s risk of falling and taking steps to reduce their risk keeping the home safe and clutter-free 5/24/2024 35

36. Reference Greenberg handbook of neurosurgery 10th edition Clinical outcome of diffuse axonal injury according to radiological grade – journal of trauma and injury https://www.jtraumainj.org/journal/view.php?doi=10.20408/jti.2018.31.2.51 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571536 5/24/2024 36

37. THANK YOU 5/24/2024 37