1. Nerve Injury & Effects

2. Learning Outcomes
At the end of this lecture the student would be able to;-
Describe functional anatomy of nerve fiber
List the common causes of nerve injury
Describe different grades of nerve injury
Define the wallerian degeneration and retrograde degeneration
Explain the degenerative changes in nerve fiber after injury
Explain the regenerative changes in nerve fiber after injury and factors affecting the regenerative process
Describe complications following nerve injury

3. Nerve cells
The neurons are the basic building blocks of the nervous system, their axons may or may not myelinated.
The myelin sheath is produced by the Schwan cells, envelops the axon except at the ends & the nodes of Ranvier
The impulse is conducted faster in myelinated than unmyelinated nerves.
possesses the capacity of self-regeneration after traumatic injury

4. Functional Anatomy of Nerve fiber
axons are bundled together into fascicles.
individual axons are surrounded by the endoneurium.
entire fascicle is ensheathed by the perineurium, which forms the blood–nerve barrier.
epineurium surrounds the entire nerve, holding these structures together.

5. Some critical Points
Neuron: The primary cell of the PNS, which is polarized and has dendrites to receive information and axons to transmit information
Nerves: Bundles of axons enclosed in specialized connective sheaths
Schwann cell: Glial cell that supports and myelinates PNS axons
Endoneurium: Collection of collagenous tissue that surrounds each individual axons and their associated Schwann cell
Perineurium: The blood nerve barrier, which is composed of concentric layers of fibroblasts that form a sheath around each fascicle
Epineurium: The collagenous connective tissue layer that surrounds the outer limits of the peripheral nerve, protecting it from external stress

6. Some critical Points
Monofascicular: Nerve section composed of one large fascicle
Oligofascicular: Nerve section composed of a few fascicles
Polyfascicular: Nerve section composed of many fascicles of varying sizes
Neurapraxia: Nerve injury characterized by a reduction or complete block of conduction across a nerve lesion
Axonotmesis: Nerve injury characterized by conduction block and interruption of axonal continuity
Neurotmesis: Nerve injury characterized by conduction block, interruption of axonal continuity, and connective tissue damage

7. Common causes of nerve injury
Transection of nerve fibre (through and through cut)
Crushing of nerve fibre
Local injection of toxic substances
Ischemia due to obstruction of blood flow
Effects of hyperpyrexia on neuron

8. Different grades of Nerve injury
Sunderland classified nerve injury based on cause & extent of damage of nerve fibre to quantify the severity of nerve injury
First degree injury
Second degree of injury
Third degree of injury
Forth degree of injury
Fifth degree of injury

9. Different grades of Nerve injury
First degree injury
Involve only transient loss of nerve function
Nerve function return within few hours after the causative factor is removed.
Cause is mild pressure on the nerve leading to local anoxia due to ischemia following obstruction of blood flow
Second degree of injury
Prolonged pressure on the nerve causing severe damage of nerve fibre but endoneural tube remain intact.
Damage of nerve followed by degenerative changes
Regeneration is possible with restoration of normal function due to intact endoneural tube

10. Different grades of Nerve injury
Third degree of injury
Severe damage of nerve fibre with interruption of endoneural tube
Most severe degree of nerve injury
Damage followed by degenerative process
Regeneration process is slow and subjective depends on favourable conditions
Forth degree of injury
Most severe degree of nerve injury with interrupted endoneural tube and disturbed organisation of fasciculi
Fifth degree of injury
Seen in complete transection of nerve fibre
Highest degree of nerve injury
Degenerative changes appears rapidly following injury

11. Nerve Injury
Injury to axon of nerve- causes of series of changes occur at
Distal to injury
Proximal to injury
Cell body
Repair of injury also initiates following the injury called regenerative process, provided conditions are favourable
Both degenerative and regenerative changes depends on degree and type of injury

12. Sequence of events following nerve injury

13. Wallerian degeneration
Degenerative changes which occur in the part of axon distal to injury.
Name derived after the scientists “A Waller-1862” who discover and identified theses changes.
Defined as process of degeneration of a nerve fiber that has been separated from its nutritive center by injury or disease,
characterized by segmentation of the myelin and resulting in atrophy and destruction of the axon.
Also called orthograde degeneration, secondary degeneration

14. Wallerian degeneration
Occur within few hours after the injury and continue for about 3 month
Axon becomes swollen and irregular in shape
Breaks up in to small segments
The neurofibrills breaks down in to granular debris
Myelin sheath start slowly to disintegrates from 8th day after the injury and finally in to fat droplets
Schwan cell begins to multiply and gradually occupies the empty neurilemmal space,
Schwan cell’s cytoplasm also proliferates rapidly to produce series of membranes which help to form numerous tubes

15. Retrograde degeneration
Degenerative changes occur in the axon of neuron, proximal to injury includes cell body and axon proximal to injury
Begins within 48 hours following injury and continue up days
Defined as Pathologic changes that occur in the axon and cell body of a neuron proximal to an axonal lesion.
The process is characterized by central chromatolysis which features flattening and displacement of the nucleus, loss of Nissl bodies, and cellular edema.
Central chromatolysis primarily occurs in lower motor neurons.

16. Retrograde degeneration
changes in axon are similar to changes seen in distal part (wallerian degeneration), following injury to axon near to first or second node of Ranvier.
Nissl granules of cell body undergo disintegration and finally results in chromatolysis.
Process of chromatolysis starts around nucleus and gradually spreads to periphery.
Golgi apparatus, mitochondria and neurofibrills fragmented and eventually disappear.
Cell body draws more fluid, enlarges and becomes spherical.
Nucleus displaced to periphery or extruded out of the cell leading to neuronal atrophy or finally disappear.

17. Factors affecting regeneration
Presence of Neurilemma- must for regeneration. Axon of CNS never regenerate as they do not have neurolemma.
Presence of Nucleus- must for regeneration to begin. In condition where Nucleus extruded out, process of regeneration does not occur.
Types of injury-process of regeneration occur rapidly in crush injury as compared to sharp cut of neuron.
Gap between injured fiber- should not increased more than 3 mm. if the gap between cut end of nerve fibers is less, then chances of regeneration are increased considerably
Rapid regeneration process occur if the cut end remains in the same line,not moved away from each other

18. Regenerative Changes
Followed by degeneration depends on favourable condition.
Occur in 5 stages
Stage of fiber formation;
Axis cylinder from proximal cut end of axon elongates and gives out fibrils upto 100 in numbers in all directions
fibrils grow in to connective tissue at site of injury and attempt to reach to distal end of axon.
Stages of entry of fibrils in to endoneural tube
Strands of Schwan cell guide the growing fibrils to enter in to endoneural tube of axon, and grows rapidly at faster rate
The fibrils which are unable to enter the endoneural tube, degenerate

19. Regenerative Changes Stage of active growth Stage of myelination
Growing axonal fibril enlarges and establishes the contact with appropriate end organ
Process of myelination not yet begin, fiber is ummyelinated
Stage of myelination
Process of myelination begins slowly and completes in one year
Progressive increases in diameter occur
Regenerated fibre attain 80% of its original diameter
Changes in Cell body
Nissl granules followed by Golgi apparatus appears
Looses excess cytoplasm to regain its size
Nu occupies central position

21. Complications following nerve injury
Complete atrophy of nerve fibre
Functional complications in the form of misinterpretation of sensation due to abnormal connection during the process of regeneration
Neuroma formation – whorls like mass which is very painful. It is due to abnormal regeneration process where gap between the cut end of nerve fibre is too large, thus leading to formation of fibers turn around for search of endoneural tube and form a mass. Common example is phantom limb