1. Nerves are the peripheral extensions of the central nervous system allowing it to deal with the outer world. Even in unicellular organisms the nucleus is wired via the cytoplasm through its reticular structures which extend up to the organisms cell membrane. Nerves that emerge from the neuronal tissue in the cranium are called the cranial nerves. Those that are connected to the neurons of the spinal cord are called ‘Peripheral Nerves’. The brachial plexus belongs to the latter system.
2. An axon which is the basic unit of a nerve is in fact a cytoplasmic extension of the neuron. Many axons make a fascicle and several fascicles make a nerve. Some nerves are uni-fascicular (one large fascicle). There are other nerves which carry very few fascicles (oligo-fascicular). Unlike in an electrical or fibre optic cable, fascicles within a nerve are known to change position. For e.g. a fascicle which appears at a nine o clock position on a cross section of a nerve at the elbow may have changed its position to six o clock or three o clock when the nerve crosses the wrist. These changes are not entirely random and have been charted to a great extent. Unlike in a non living electrical or fibre optic cable system, fascicles change course entering adjacent bundles forming a grid which helps preserve function in a partial injury to the nerve. The axon is wrapped in connective tissue called endoneurium. The corresponding layer for the fascicle is the perineurium and the nerve itself is enveloped by the epineurium which sends septa separating the fascicle. This connective tissue is elastic and is thicker where nerves cross joints to allow movement.
3. The neuron has a shorter cytoplasmic extension called the dendrite which connects it to other neurons but it is also in contact with axons as well as the parent neuron through synapses. A neuron is remarkably different from the other cells in the body in that it has several outcrops called ‘boutons’ which form the eyes and the ears of the neurons and are connected to these synapses.
4. Peripheral nerves at their spinal end are called roots. The ventral roots are those which arise from the ventral and lateral neuronal tissue of the spinal cord and are motor in nature including a vasomotor component. The dorsal roots receive the sensory nerves but are different from the motor efferents in that they have a spinal ganglion outside the bony spinal structure which contain additional modified neurons (also called inter-neurons) with their own dendrites which connect these neurons to each other. A mixed nerve is called as such when both motor and sensory nerve channels travel together.
5. A bulk of the axons are insulated by a sheath of myelin (myelineated axons) which is made up of proteophospholipids arranged in multiple spiral layers which are derived from the Schwann cells which are like sub stations of the parent neuron and these two cellular structures namely the Schwann cell and the neuron, communicate through the axon. This arrangement therefore is uniquely integrated and far more alive than other linear structures in the body.
6. The insulation of myelin ensures that there is no wastage of the signal conduction that the axons carry and even smaller nerves can be more efficient.
7. A myelineated axon is divided into segments at the ends of which myelin is absent. This area is named after Ranvier. A single Schwann cell envelopes the axon between the two nodes of Ranvier.
8. While conduction of an impulse in an axon occurs by linear molecular movement called slow conduction, conduction also occurs in spikes or leaps (saltatory). The generation of electrical currents is a function (like elsewhere in the body) of the change in the permeability of the cell membrane which is normally ‘gated’ with sodium ions in the extracellular space and the potassium ions within. When sodium ions enter the cell and the potassium exits the cell, depolarization is said to occur. When an electrical discharge is complete, sodium ions get pumped out and potassium flows in passively. The nodes of Ranvier are the sites where these spiked potentials are generated for communication to either side. The node has a higher density of mitochondria which supply the energy for both polarization as well as depolarization.
9. All nerve fibres are not myelineated (though the bulk are). The unmyelineated fibres are enveloped in their entirety by a chain of Schwann cells, their walls abutting each other closely by apposition. Conduction along unmyelineated fibres consequently is less efficient and is proportionate to their cross sectional diameter.
10. Because peripheral nerves are integral to survival from any adverse environmental change, they are high-metabolic structures. The metabolism is entirely aerobic and therefore their blood supply is functionally critical. The extrinsic supply to a nerve comes from branches of major arteries in the vicinity and also from branches of muscular or periosteal vessels. Then they run along and within the epineurium, send proximal and distal branches and therefore help to form a plexus.
This plexus then forms the intrinsic system with numerous anastomosis between arterioles and venules and the flow within this arrangement is not unidirectional. The segmental nature of the blood supply of a nerve is such and the sub-epineurial plexus formation is so widespread that trauma to the extrinsic blood supply over some length does not devascularise the nerve as long as the axial epineural and sub-epineurial plexus is not damaged. However, prolonged traction causing elongation between 8-15% will halt the blood supply leading to damage to conduction. From this it also flows that the intrinsic plexus around the fascicles can sustain them even if they are dissected for some length away from the epineurial vessels and they remain as viable units. The endoneurial capillaries are comparatively broader as compared to the other capillaries but are somewhat segregated from the epineurial plexus and contain large volumes of blood as a reservoir confirming the high metabolic nature of this tissue.
11. As is expected, the glabrous or non-hair bearing skin of the sole or the palm has the highest number of sensory receptors as well as free nerve endings in the body. This skin also has a thick epidermal cover which dips into valleys and therefore also has corresponding ridges. The dermis is insinuated into this arrangement and is called the papillary layer of the dermis.
12. The nerves of the skin are both myelineated and un-myelineated and form a subdermal, deep dermal and papillary (at the junction of dermis and epidermis) plexuses from which various nerves proceed to receptor organs for carrying the afferent impulses. In the non glabrous skin free nerve endings also supply the hair follicles and these might be unmyelineated.
13. Of the receptors, Meisners’ corpuscles occupy the dermal papillae and the deepest layers of the epidermal projection and perceive flutter, vibrations and moving touch. The Merkell cell-neurite complex at the epidermo-dermal junction feels constant touch and pressure. The Ruffini’s corpuscle, located throughout the dermis, specializes in detection of position and velocity and the Pacinian corpuscle located sub-dermally is mainly a pressure receptor. Awareness of one’s skin without any stimulation becomes possible because of the basal resting electrical potential within these receptors.
14. Hair and hair follicles are innervated both by myelineated and unmyelineated fibres which convey sensations because of the fine disturbance that the movement of hair causes in the follicle as well as a coarser movement of the hair follicle itself when the skin is deformed.
15. Free nerve endings of both types are present in large numbers throughout all layers of the skin and mainly convey cold and warmth as well as pain, fine tickling sensation as well as that of itching.
16. Afferent impulses arise in the receptor area due to mechanical or ionic changes caused by e.g. heat causing a shift in the balance of cell membrane potentials.
17. While this general anatomical arrangement continues to be replicated in the mucocutaneous junctions as well as the exposed parts of the mucosa, the genital mucocutaneous junctions and their periphery exhibit a very high incidence of free nerve endings as well as a special end organ called Krause’s bulb which is similar to but a slight variant of the Meisner’s corpuscle.
18. The sensory innervations also extend to muscles, tendons, joint capsules, ligaments and the periosteum and they perceive deep sensibility, the sense of position, stretch and tension. In the muscles the receptors are spindle shaped and convey these sensations via heavily myelineated fibres and are connected to receptors in the tendons which are called Golgi bodies and are similar to the Roufini receptors of the skin. Other receptors very similar to the ones in the skin (Pacinian corpuscles) are in abundance in joints, capsules, synovial sheaths, interosseus membranes and are sensitive to acceleration and vibration. In addition free nerve endings which carry the feeling of pain are present in the synovium and joint capsules. The spindle shaped receptors of the muscles are modulated via a centrifugal efferent nerve connection with its external or extra fusal member which then gauges the length, tension and stretch within the muscle fibres, the two together being responsible for coordination and the ultimate contraction of the muscle.
19. The motor end organs or the end plates in the muscle are innervated by a myelineated nerve fibre which breaks into several unmyelineated axons which then lie in a trough along the muscle fibre and are covered by Schwann cells at what is known as a synapse. This area is filled with mitochondria which help supply the energy to change the electrical potential around the axonic cell membrane, resulting in a stimulus to the muscle which contracts because acetylcholine is released from vesicles located around the motor end plate. To summarise, the contraction of a muscle occurs through a stimulus by motor nerve endings, in turn directed by the spinal neurons and the brain and is determined by the position, stretch and tension within the muscle as communicated between the extra fusal and intra fusal muscle end plates which also have a sensory inter communication in between them.
20. Diseases of the nerves are not the province of a surgeon (plastic) but disruptions of nerves by other causes principally injuries or compressions are treated by surgical specialists including plastic surgeons. Leprosy and diabetic neuropathies with consequent effects however are two exceptions where plastic and other surgeons have principally contributed through decompression of nerves as well as reconstruction of nerves and the deformities that these diseases might cause.
21. An injury to a nerve can either be in the form of a temporary functional block in a short segment (neuropraxia) which recovers rapidly (within weeks) or involves anatomical disruption of axons which remain in continuity without disturbing their connecting tissue envelope (axontmesis). In the next category the axonal continuity is severed together with its envelope and recovery is impossible unless co-option of the severed ends is achieved. This is the severest form of injury and is called neurotmesis. This classification of Seddon has been enlarged by Sunderland to take into account the fascicular nature of nerves and their severance. It is to be noted that many nerve injuries are likely to be a mixture of all three types where adjacent areas of neuropraxia and axontmesis might be present when the nerve is severed.
22. When nerves are injured the distal axons degenerate and the end organ (sensory or motor) undergoes changes in which its supportive structures atrophy depending on their lifecycle, ultimately leading to complete degeneration of the end organ itself. From here on reinnervation becomes impossible. However if axonal regeneration occurs before the end organ becomes extinct, reinnervation is possible in varying degrees as the supporting tissue gets relaid. Pending reconstruction of a nerve, a deinnervated muscle can be subjected to intermittent electrical stimulation in order to maintain its membrane potential.
23. When an axon is severed, the distal axon disintegrates together with its myelin sheath reaching up to the end plate. Proximally the fragmentation halts at the next node of Ranvier. The corresponding neuron perceives this change and alters its strategy and downgrades the function of conduction of impulses and upgrades its regenerative function. Synaptic transmissions reduce and the boutons withdraw within the neuron. The riboxynucleic acid content rises, protein synthesis takes precedence over conduction activities and the level of substances needed for transmission falls.
24. Within as early as 24 hours the severed proximal end of the axon forms a bulging growth cone which advances together with axonic growth collaterals from not only the immediately proximal node but also from up to several segments before it and reaches the zone of injury. This development is a throwback to when axons were progressing towards their destination during embryonic development. When an axon establishes contact with its distal injured counterpart and succeeds in entering the distal axonal tube, it’s collaterals withdraw or degenerate. As the axon enters the distal endoneurial sheath, Schwann cells are seen growing around the axon in the proximal to distal direction. Myelineation is replicated if the original axon had the advantage of myelin cover. The biological by products of these reconstructive efforts are transported back to the neuron through the peri-axonal space.
25. What prevents the axon from entering the distal intra-neurial space, is a scar or the ever present post-injury extracellular matrix. Axonic collaterals are advantageous in this situation allowing a multiple choice for penetration. Though not conclusively proved, some evidence has emerged that the growth cone might have enzymatic products which help the axons to burrow through the scar or the extra cellular matrix.
26. What is crucial to this axonal advancement is the patency of endo-neurial space in the distal part of the injured nerve. Schwann cells start clearing the area of myelin sheath and form longitudinal rows to maintain this endo-neurial space but their very survival is dependent on the original axonal continuity. If axons do not penetrate this new space, collagen, the ever ready ‘filler’, slowly occupies this space as a part of general repair and nerve regeneration fails partly or completely.
27. Even when axonic penetration is successful, the endo neurial space is usually not of the same diameter and therefore the axonic diameter has to reduce and the inter nodal distance in the newly penetrated axon is also reduced. The rate of axonal growth depends on the distance between the site of injury and the corresponding neuronal cell. The longer the distance, the slower the growth. Injuries in the upper arm will heal faster as compared to those at the wrist if the conditions and the nature of injury are identical. On the other hand a proximal injury means that the axonal damage occurs in fascicles, which are not yet end organ specific, and because post injury axonal penetration must remain a random event, restoration of end organ function might be that much poorer. A nerve in the palm or foot in comparison is more ‘end organ’ specific with fewer axons and therefore, though axonal penetration might begin later (by the above law), the end result might be more satisfactory notwithstanding some randomness of axonal penetration.
28. In the severe forms of nerve injuries, the degree of retraction of axons is a function of the integrity of the epineurial tissue which disallows too much withdrawal by virtue of constraints of space as well as the septa that run across from the epineurium. The spontaneous natural repair in such circumstances is possible but will remain quite unsatisfactory even though the axons will penetrate the natural scar in the zone of injury resulting in an entity called neuroma in continuity which is a jumble of axonal sprouts entangled in a scar some of which might have entered the distal axonal tubes.
29. In the severest forms with extensive laceration, spontaneous regenerative reinnervation invariably fails particularly when the severed nerve ends lie at some distance from each-other.
30. Some points are noted below:
a. The greatest impediment to repair of nerves is a scar that will obstruct axonal penetration.
b. The random nature of axonal penetration even when meticulous surgical coaption is achieved will adversely affect the end result. This is particularly true of a mixed nerve though it must be noted that what we call a pure motor nerve is in a way a mixed nerve because it carries proprioceptive and autonomic sensory components.
c. Early repair is crucial so that the distal deinnervated systems together with the end organ do not lapse in to a state of irretrievable state of atrophy and loss of function.
d. Yet adequate treatment of associated injuries, particularly vascular injuries and fixation of unstable fractures, must be carried out prior to or together with repair of nerves.
e. A good vascular uncontaminated bed helps regeneration of nerves. The results of repair of nerves are best in the younger patients and the results slowly deteriorate with age. Unlike in tendons, repair of nerves can be undertaken even if the flap cover is being done in two stages, in the first stage itself as long as the wound is reasonably well closed.
f. A proximal injury nearer the neuron has a greater destructive influence on the neuron and consequently its reparative process suffers.
g. Axon avulsion from the cell membrane of a neuron is almost fatal to a neuron and therefore repairs are impossible and the surgeon might have to opt for muscle and tendon transfers to restore function. Post-ganglionic disruptions fare far better in this regard.
h. Notwithstanding what has been narrated, the results of repair for injuries to nerves which supply major muscles for e.g. shoulder girdle, though they are nearer the neuron, may have a gratifying result because their movements are coarse and are judged as such. On the other hand repair to nerves to distal smaller muscles, e.g. the lumbricals and the interrossi in the hand, will show that, though the co-option of the severed nerves have a lesser chance of displaced axonal penetration, the results might appear unsatisfactory If looked at critically because the functions of these muscles are more intricate and finely calibrated. However these procedures continue to be very gratifying vis a vis clinical results.
31. Reinnervation of a muscle when it occurs gives the best results when the deinnervated muscle is nursed in a satisfactory state by electrical stimulation and physical therapy, because an atrophied muscle not only becomes smaller in size but is progressively replaced by connective tissue and, by two years, few muscle fibres are recognizable. Even after the motor end plate is reinnervated a lag period is noticed of about two or three weeks before direct stimulation of the nerve produces an adequate muscular contraction. It has been mentioned earlier in this chapter that two parallel intra fusal and extra fusal spindle shaped motor end plates coordinate with each other through their additional inter connected sensory function in gauging the length, strength and position of muscle fibres, the intrafusal end plate sending afferent fibres to the extra fusal end plate. Even in ideal conditions neurotisation may be not be able to restore this connection fully, resulting in a not so perfect return of function.
32. In the skin the Merkel cell neurite degenerates the fastest while the Pacinian corpuscle survives for the longest period. The Miesners’ corpuscle occupies the middle position in this regard. The return of sensory function is dependent on the surviving sensory end organs as well as axonal sprouting and regeneration. Most of the studies in this regard have been done on skin grafts and there is evidence that there might be some specificity when it comes to reinnervation when glabrous and hairy skin are interchanged in an experiment where the bed from which axons will sprout remains the same. A bed that originally supplied sensory modalities of hairy skin does better when hairy skin is transplanted on the bed and vice versa. In any event the varying rate of degeneration of the different receptors and the problems of random penetration by axons usually means that a return to almost normal sensibility is rare when this sensibility is tested with high precision. An additional problem in monkeys and man is the functional rigidity of the cortical sensory zones. If the peripheral reinnervation is not exact the cerebral reception is confused and an accurate perception becomes difficult. The cortical areas in the lower animals are more flexible in this regard and the return of sensation in them is far better even if the reinnervation is crossed.
33. Because a nerve transmits its impulses by way of an electrical discharge caused by a series of depolarizing/repolarising events, its functioning can be best studied by electro diagnostic tools.
34. This is done in two ways
a. By sending a current along the length of a nerve and studying its speed and / or locating at which place this current gets impeded or stops completely in its progress. This is called the study of nerve conduction velocity.
b. By studying the effects of this current directly on an end organ like a muscle which is called electromyography.
35. Nerve conduction velocity is measured by putting two electrodes at some distance on a nerve, one of which will be near the end organ and the other further away. What gets tested is the segment between the two electrodes. One of the best applications of this method is to be able to diagnose a compression neuropathy (for e.g. Carpal tunnel syndrome). Nerve conduction velocity can also diagnose multiple areas of compression by moving the electrodes along the length of the nerve. This method is best applied to larger nerve trunks with larger faster axons and is unsuitable for small fibre neuropathies.
36. Electromyography employs small needles which penetrate a muscle and test its electrical potential. In a normal resting state, the muscle will not exhibit any electrical activity. Deinnervation of the muscle causes an abnormal secretion of acetylcholine leading to small contractions of muscle fibres or fibrillation which these needles will record. The time lag for the fibrillation to appear is a function of the location of the nerve injury. The nearer the injury, the earlier the fibrillation. If the injury is distant, distal axonal degeneration takes that much longer and fibrillation will start occurring several days or weeks from the time of injury. The presence of fibrillations is diagnostic of deinnervated but living muscle and indicates that reinnervation can be undertaken and might succeed. After reinnervation its success at the motor end plate can be gauged by the response of the muscle on stimulating the nerve proximal to the site of repair (or decompression) by the appearance of polyphasic potentials or waves.
37. After what was a depressing era in which the results of repairs of nerves showed very little benefit, in the last fifty years with better understanding of the physiology of how nerves respond to injuries and their fascicular arrangement, repair of nerves is viewed with far less gloom than before. The advent of the operating microscope has played a major role in this transformation.
38. Because the results of surgical coaption have been indifferent in the past and also because these failures were attributed to the scarring that surgical apposition invariably caused, the technique of placing the two cut ends of the nerve, after pre-operative preparation, close to each other in a living conduit (eg. a vein or an artery) or a non- living tube, for example rubber or tantalum, has been tried over several decades but has not shown to be any better than a standard surgical coaption.
39. In fact there is little unanimity amongst surgeons even about the superiority of fascicular repair (perineurial) over an epineurial repair. With the arrival of a biological glue by which properly aligned ends of nerves are apposed to each other and then treated and fixed with this adhesive, a new era might be being unveiled in this respect. The alignment of the nerve with the corresponding fascicles properly facing each other is crucial whatever the form of repair. In this respect in the larger nerves the axial epineurial vessel which runs on the body of the nerve is greatly helpful to align the nerve properly. The exact topography of fascicles in individual nerves as well as their stimulation to ascertain their effect on distal end organs or to elicit sensory feelings is beyond the scope of this text.
40. Whatever method is employed to coapt nerves the aim of the surgeon is to fashion nerve ends which are free of scar. Having removed the scar, the nerve ends must appear to be alive (altogether a difficult thing to gauge precisely) from which fascicles must not be hanging too far out from the epineurial edge. The elimination of scar or debris or dead crushed fascicles or a neuroma begins at some distance from the injury by a longitudinal incision along the length of the nerve in the epineurium. The epineurium having being incised, some fine dissection can enter a deeper intra-fascicular plain. This then is carried towards the severed ends. By training, observation, a tactile impression of how the tissue cuts and with the help of magnification it is possible to identify the last living post (!) of the nerve at both ends. This recognition however remains mainly empirical and has a learning curve. The freshening of nerve ends is left to the very end when all scar and non viable tissue is sectioned off and repair must begin quickly. The other commonly used method is to take transverse cuts across the nerve beginning from the injured end till normal scarless fascicular bundles are seen.
41. When repair is finally undertaken, the sutures must hold easily (no tension) and the nerve must itself lie comfortably on an unscarred vascularised bed (without being taut or getting blanched even when the part is put through its normal motion). The apposition (fascicular or epineural) must not be such that repaired neural tissue tends to buckle and appears to be too far prolapsed from its epineurial sheath prior to suturing.
42. If there is tension when the ends of the nerve are apposed (this can be gauged when the nerve is being prepared for suturing) some trimming of mesoneurium can be undertaken on either side to gain slack. The choice of the caliber of the suture material is 100 for fascicular repair and 80 for epineurial repair. In order to achieve non-traumatic repair of fascicles “tension freeing sutures” of up to 70 or 80 can be temporarily placed on the epineurial tissue. These effect easy apposition of the fascicles and they then can be replaced with final sutures. Though the new biological glue now appears poised to replace elaborate and labourious suturing.
43. Tension, infection and foreign body interference near the axons will invariably mar the end result.
44. Notwithstanding the controversies about when an injured nerve should be repaired, two practices are now universally accepted.
a. An iatrogenic injury to the nerve at the time of a planned surgical procedure (e.g. the trunk or the branch of a median nerve while releasing a carpal tunnel compression) or an otherwise clean transection of a nerve or nerves with or without injury to tendons should be repaired primarily within several hours.
b. In the other extreme category for e.g. an indiscriminate war wound involving penetration and / or a blast effect with other injuries such as fractures in the same zone further complicated by contamination and the need to treat other parts of the body to stabilize the patient, a delay becomes inevitable because,
i. The patient needs to be stabilized, the fractures need to be fixed and vascular restoration might need to be undertaken
ii. The nature of the nerve injury might be of a complex nature over a length including axontmesis and neurotmesis, patches of devascularisation or as in a bullet wound, a friction or a thermal burn.
45. The exact nature and extent of such an injury becomes apparent several weeks later both clinically as well as by electrophysiological methods. The waiting period in such cases cannot of course be extended to four or six months. The old thinking that old injuries can be repaired even after a year or several years is not accepted any more. Injuries to nerves under the above circumstances might involve excision of dead nerve tissue over several centimeters, will require careful mobilization before coaption can be achieved without tension. These are the kind of cases that might need to be treated with nerve grafts.
46. Nerve grafting becomes necessary when coaption is not possible. The commonest nerve harvested is the sural nerve though for small gaps in digital nerves the terminal portion of posterior interosseous nerve is useful. The medial cutaneous nerve of the arm is another choice. The preparation proceeds in the same manner as for coaption. The repair is however staggered in that the fascicles are cut at different levels both in the proximal and distal ends to avoid a common scar. The nerve graft is not used as a single strand but is dissected into fascicles which are joined individually and the end result does not appear like a single nerve unit but an array of strands spread across some millimeters. The requirements for coaption and nerve grafts vis a vis the nature of bed including its vascularity as well as the post-operative care are not different. A 100 suture is most suitable for this purpose and the problem of tension does not arise if adequate donor nerve is harvested.
47. Vascularised nerve grafts have been tried recently especially for large proximal severed nerve trunks surrounded by poor vascular beds and there is experimental evidence to suggest that the rate of reinnervation is better than ordinary grafts. The sural, superficial radial or the saphenous nerves have been used for this purpose. Pedicled vascularised nerve grafts have also been tried. The vascular supply of these grafts runs along the epineurial vessel and grafts are chosen when a single dominant vessel supplies the nerve (e.g. the ulnar nerve from the middle of the arm to the wrist is supplied by a single dominant vessel and can be harvested in this entire length). Post operative care of these procedures needs to be even more exacting and has to be very gentle and precise because of the size of the micro anastomosis.
48. Though surgery on nerves might not be a major component of an average plastic surgeons workload, this chapter has been written at some length because it reveals fascinating details of how elegant and efficient nature is vis a vis the structure, function and attempts at repair that the body undertakes when it comes to nerves.
Dr. Visweswar Bhattacharya from Varanasi adds as an adjunct to point 23 as follows:
In the event of a nerve injury, the axons proximal to the injury relay information to the corresponding neurons. The cell body is located within the spinal cord (motor nerve cell) or posterior root ganglion (sensory nerve cell). They swell in size, reflecting a greater enzymatic activity, increase in the overall content of the amino acids, transformation of the RNA to a more active state and a rise in the quantity of nucleic acid. Proteins formed as a consequence of this activity are transported to the site of the nerve injury to help in the process of repair. Such a neuronal regenerative contribution is dependent upon the distance between the site of the injury and the neurons. In an injury at the wrist to the ulnar or the medial nerve, the reparative neuronal activity for example will continue for 60-90 days.