Injuries of Peripheral Nerves

Injuries of Peripheral Nerves

CHAPTER 11

11

11.1 Anatomy 241

11.2 Types of Morphological Reactions 242 11.2.1 Wallerian Degeneration 242

11.2.2 Retrograde Reaction (Axonal Degeneration) 242 11.2.3 Remote Effects 242 11.2.4 Edema 243 11.2.5 Regeneration 243

11.3 Types of Injury 243 11.3.1 Injuries

by Compression and Percussion 243 11.3.2 Injuries

by Traction and Elongation 243 11.3.3 Injuries by Transection 244

Bibliography 244

References 244

Peripheral nerve pathology is of minor importance in forensic pathology since lesions of the peripheral nerves rarely cause death. Patients with peripheral nerve symptoms generally consult neurologists and neurosurgeons. Diagnosis following biopsy com- monly will be performed by the clinical neuropathol- ogist. However, because forensic neuropathologists are sometimes asked to give their opinion in cases involving physical injury of the peripheral nerves, we will deal with this topic briefly. For information regarding specific questions, the reader is referred to the Bibliography.

11.1 Anatomy

Peripheral nerves contain myelinated and unmyelin- ated axons from different types of neurons, subserv- ing various motor effector functions or acting in a sensory function. The peripheral nerves include all except the first two pairs of cranial nerves, as these

are more properly considered tracts, containing oli- godendrocytes rather than Schwann cells. The neu- ral components of the anterior spinal roots are motor fibers, those of the dorsal roots are sensory. The sen- sory fibers of the dorsal roots possess cell bodies that reside in the posterior root ganglia. The spinal roots fuse to form mixed nerve trunks. The lower cervical and lumbosacral regions contain plexuses of nerves, while the thoracic region is where preganglionic myelinated fibers from neurons in the lateral horns of spinal cord gray matter leave the anterior roots en route to the paravertebral chain of sympathetic ganglia or the splanchnic nerves. The preganglionic parasympathetic fibers pass out of the anterior spi- nal roots in the pelvic region and in the third, ninth, and tenth cranial nerves. The parasympathetic gan- glia are located in or near their effector organs.

An outer connective tissue sheath, the epineu-

evident in transverse histological sections of the nerve (see Bischoff and Thomas 1975). Most moder- ate-sized nerves possess a single main muscular ar- tery that runs longitudinally along the nerve within the epineurium. A perineural sheath with concentric layers of flattened cells separated by layers of colla- gen surrounds each nerve fascicle. The endoneurial compartment of nerve fibers is enclosed by a peri-

tains blood vessels, Schwann cells, and bundles of endoneurial collagen fibers oriented longitudinally along the nerve fascicle. Cylindrical hyaline Renaut bodies are normal features of nerve, and are located in the endoneurial compartment (Asbury 1973; Dyck 1975).

Myelinated fibers are best demonstrated in par- affin sections stained for myelin with Luxol fast blue, Loyez or Heidenhain‘s hematoxylin techniques. Al- though it is difficult to satisfactorily visualize non- myelinated axons in paraffin transverse sections of nerve, they can be stained by silver techniques (Bo- dian technique) and followed in longitudinal sec- tions.

Transverse sections show the myelin sheath to be

a tube surrounding the axon that extends along the

nerve fiber from a position near the cell body and

ceases 1−2 µm from the peripheral axon terminals.

242 PART II: Physical Trauma

Myelinated nerve fibers are divided into segments, each the length of a single Schwann cell and its re- spective myelin sheath. The axon is continuous from segment to segment, nodes of Ranvier marking the junctions between segments and the small gap be- tween Schwann cells.

The thickness of the myelin sheath of normal peripheral nerves is proportional to the axonal di- ameter. Measured in transverse sections, this feature can help in detecting axons that are remyelinating following segmental demyelination if they possess disproportionately thin myelin sheaths.

A surface membrane, the axolemma, bounds the axon and is its cell membrane. Both neurofilaments and microtubules can be detected by electron mi- croscopy. The axoplasm contains mitochondria and vesicles or elongated profiles of smooth endoplasmic reticulum.

11.2

Types of Morphological Reactions

Two general types of peripheral nerve degeneration are known, axonal and demyelinating. The processes of nerve fiber repair differ according to the type of lesion. Although peripheral nerve fibers have a strik- ing capacity to regenerate and Schwann cells to re- myelinate demyelinated or regenerated nerve fibers, it appears that the structural restoration is not com- plete. The degeneration and regeneration processes involve endoneurial connective tissue and myelin sheaths as well as axons, Schwann cells, and macro- phages (for details, see Chap. 4.3, pp. 56 ff). The ba- sic principles should be concisely repeated.

11.2.1

Wallerian Degeneration

The process of Wallerian degeneration (p. 66) refers to degeneration of the axon isolated distal to a cut of the axon from the nerve cell body. It includes axo- nal and myelin sheath changes as well as the reac- tions of local and hematogenous cells. Nerve fibers of the distal stump of transected nerves degenerate, while fibers of the proximal stump survive and are capable of regenerative outgrowth. If the nerve is completely transected, Wallerian degeneration in its most developed form occurs distal to the lesion. The axonal changes, however, are closely associated with Schwann cell changes that are much more compli- cated in myelinated than in unmyelinated nerve fi- bers. The degenerating myelinated nerve fibers vary considerably in their morphology depending on the interval after the traumatic event, distance from the lesion, and the part of the internode studied.

The first changes appear to involve an accumu- lation of organelles near the proximal and distal stumps of the transected fibers. As the distal part of the axon degenerates, a series of structural changes occur that ultimately lead to axonal fragmentation and dissolution. Then, 36−96 h after nerve crush, numerous discontinuities can be noted in the axo- lemma together with focal swelling or condensation of axons, dilatation of the axoplasm, zones of in- creased density and granularity, and dissolution of neurofilaments and microtubules (Webster 1962).

Emigrating macrophages accumulate (Dyck et al.

2003).

Axonal changes are closely associated with sec- ondary myelin or Schwann cell alterations. Frag- mentation at the Schmidt−Lanterman incisures coincides with retraction of the myelin loops at the node of Ranvier and folding, contraction, and exten- sion of myelin sheaths.

11.2.2

Retrograde Reaction (Axonal Degeneration)

Retrograde reactions involve (p. 66) sequences of events in myelinated fibers that are associated with complete degeneration of the affected neurons (neu- ronal degeneration) or of their distal processes (distal axonal degeneration or dying back). In distal axonal degeneration (Dyck 1975), there is a slight decrease in axon caliber with loss of neurofilaments, but relatively good retention of microtubules. More pro- nounced changes are associated with intoxication, characterized by a so-called dying back phenome- non involving nerve fiber degeneration. Neurons are preserved, but the distal ends of the nerves degen- erate. „Dying back“ neuropathy is encountered in a number of toxic neuropathies, such as acrylamide and organophosphorus poisoning (Cavanagh 1979).

11.2.3

Remote Effects

Remote effects of peripheral nerve injury include

proximal neuronal alterations (chromatolysis) and

neurogenic muscle atrophy. An axon injured near

the neuronal perikaryon undergoes chromatolysis

(Fig. 3.1c). The earliest change is a proliferation of

microglia around the neurons (Prineas and Spencer

1975). The neuronal cell body starts to swell, neu-

rons lose most of their synapses, the Nissl substance

(ultrastructurally, stacked granular endoplasmic re-

ticulum and polyribosomes) migrates to the cell pe-

riphery, and the center of the cell is deprived of much

of its staining by a regenerative process. Muscle at-

CHAPTER 11: Injuries of Peripheral Nerves 243

after axonal degeneration, the muscle fibers atro- phy, groups of atrophic muscle fibers lying between groups of normal muscle fibers. The atrophic fibers are greatly reduced in diameter.

11.2.4 Edema

Wallerian degeneration after nerve crushing or curving is associated with increasing permeability of the blood−nerve barrier. The breakdown peaks in the distal parts about 8 days after wounding (Olsson 1975), when regeneration begins. Blood−nerve func- tion is fully restored within about 30 days (Seitz et al. 1989).

11.2.5 Regeneration

The peripheral nervous system is surprisingly resil- ient, although there are certain limitations to nerve regeneration. The degree of recovery is determined by the type of lesion, its site in relation to the peri- karyon, the patient‘s age, and whether and to what extent function can be restored (Schröder 1999). Re- generation is only possible if the nerve‘s endoneurial and perineurial connective tissue is largely intact and if optimal pathways to guide the regenerating axons to their original destination are provided by the bands of Büngner.

The reactive sprouting as a reaction of axonal in- jury appears to reflect an intrinsic neuronal response pattern (Hall 1989). The subsequent organization of the sprouting, in particular the orderly growth of mini fascicles toward the distant distal stump, does not occur in the absence of Schwann cells, which re- spond to axonal stimulation by temporary upregula- tion and re-expression of molecules to form a suit- able substratum for axonal growth.

11.3

Types of Injury

Mechanical violence or other types of physical and chemical insult can damage the peripheral nerves:

compression, transection, laceration, stretch, cold, heat, electricity, irradiation, and poisoning. Physical lesions usually result from an accident or are induced iatrogenically (Stöhr 1980) by injections, operations, bedding or irradiation. Clinically paresthesias pre- dominate initially, followed by hypoesthesias and still later by anesthesias and motor paralysis. Char- acteristic types of peripheral nerve injury as por-

trayed by Schröder (1999) and others are described in the following.

11.3.1 Injuries

by Compression and Percussion

Their long and superficial course makes the periph- eral nerves especially susceptible to mechanical violence. Compression of sufficient magnitude and duration can injure axons (Aguayo 1975). Peripheral nerves subjected to forceful percussion, e.g., by a blow from a blunt object or by vibrating instruments, and compression against underlying bony structures can suffer axonal damage resulting in Wallerian de- generation distal to the site of injury.

The clinical feature is characterized by parasthe- sias within 1−2 min. Within 1 or 2 min of compres- sion also morphological changes are to be seen: the border fibers of fascicles are edematous and more affected than centrally located fibers. Usually there is no or little transection of nerve tubes (basement membrane), perineurium, blood vessels, and epi- neurium. Therefore, transected axons can regrow to previous targets (Dyck et al. 2003). The primary in- jury is followed by marked periaxonal and intramy- elinic edema with segmental demyelination leading ultimately to axonal discontinuity (Krivickas and Wilbourne 1998). Chronic nerve compression and strangulation induces swelling of proximal axons and nerves with slight thickening of the perineurium (Mackinnon et al. 1986). The superficial nerve fibers appear to protect deeper fibers. Early reactions in- clude segmental demyelination (with remyelination) and axonal degeneration (with regeneration) as well as paranodal myelin sheath intussusception (Ochoa et al. 1972).

11.3.2 Injuries

by Traction and Elongation

Stretching of the nerve trunk, nerve plexus, and spi- nal nerve roots can irreparably tear the nerve roots away from the spinal cord, with consequent degen- eration of peripheral nerve motor axons. Because the lesion is located centrally to the spinal ganglia, the afferent (centripetal) and presumably also periph- eral (centrifugal) sensory axons and their cell bodies remain intact despite a loss of sensation (Schröder 1985).

Peripheral nerve injury is the most common in-

jury incurred by infants during childbirth. Over-

stretching of the nerves, usually because of extreme

lateral traction, can damage the brachial plexus.

244 PART II: Physical Trauma

This may occur in breech delivery when the head is delivered or during cephalic deliveries as the shoul- der is luxated free. The upper roots are the part of the plexus most vulnerable to stretching. Brachial plexus lesions mainly affect large infants with fetal depression who are subjected to abnormal labor and delivery. Proximal upper limb involvement, known as Erb‘s palsy, accounts for about 90% of brachial plexus lesions.

Klumpke‘s palsy is associated with injury of the brachial plexus and can lead to Horner‘s syndrome;

i.e., combined ptosis, anhidrosis and miosis, because it affects the sympathetic branches originating at T1.

Sympathetic injury can also disturb pigment for- mation in the iris, affected eyes remaining blue for months or years.

Slight elongation of nerves can cause temporary stimulus conduction block (Seddon 1975) lasting several hours. If the elongation is more severe, it can disrupt axonal continuity and possibly lead to tear- ing of the neural connective tissue and intraneural bleeding. Regeneration is hindered by the attendant intraneural fibrosis.

11.3.3

Injuries by Transection

The total separation of all constituents of the nerve, i.e., epineurium, blood vessels, perineurium, col- umns of Schwann cells and nerve tubes, results in a severe misalignment of nerve tubes. Either the re- generation process is totally frustrated, or the regen- erating neurites grow into the nerve tube of a differ- ent functional fiber, and, assuming that such a fiber regrows to the target, it may not be able to make a functional innervation and so presumably dies back.

The regeneration may be misdirected. From the clinical point of view, in spite of the misdirected re- generation often a delayed functional adaptation is possible.

Bibliography

Dyck PJ, Thomas PK, Lambert EH (eds) (1975) Peripheral neuropa- thy. Saunders, Philadelphia, Pa.

Schröder JM (1999) Pathologie des Nervensystems VIII. Patholo- gie peripherer Nerven. In: Doerr W, Uehlinger E (eds) Spezi- elle pathologische Anatomie, vol 13/VIII. Springer, Berlin Hei- delberg New York

Weller RO, Cervós-Navarro J (1977) Pathology of peripheral nerves. Butterworths, London

References

Aguayo AJ (1975) Neuropathy due to compression and entrap- ment. In: Dyck PJ, Thomas PK, Lambert EH (eds) Peripheral neuropathy. Saunders, Philadelphia, Pa., pp 688−713 Asbury AK (1973) Renaut bodies: a forgotten endoneural struc-

ture. J Neuropath Exp Neurol 32:334−343

Bischoff A, Thomas PK (1975) Microscopic anatomy of myelinated nerve fibers. In: Dyck PJ, Thomas PK, Lambert EH (eds) Periph- eral neuropathy. Saunders, Philadelphia, Pa., pp 104−130 Cavanagh JB (1979) The „dying back“ process. A common denom-

inator in many naturally occurring and toxic neuropathies.

Arch Pathol Lab Med 103:659−664

Dyck PJ (1975) Pathologic alterations of the peripheral ner- vous system of man. In: Dyck PJ, Thomas PK, Lambert EH (eds) Peripheral neuropathy. Saunders, Philadelphia, Pa., pp 296−336

Dyck PJ, Dyck JB, Giannini C et al (2003) Peripheral nerves. In: Gra- ham DJ, Lantos PL (eds) Greenfield‘s neuropathology, vol 2.

Arnold, London, pp 551−673

Hall SM (1989) Regeneration in the peripheral nervous system.

Neuropathol Appl Neurobiol 15:513−429

Krivickas LS, Wilbourne AJ (1998) Sports and peripheral nerve in- juries: report of 190 injuries evaluated in a single electromy- ography laboratory. Muscle Nerve 21:1092−1094

Mackinnon SE, Dellon AL, Hudson AR, Hunter DA (1986) Chronic human nerve compression − a histological assessment. Neu- ropathol Appl Neurobiol 12:547−565

Ochoa J, Fowler TJ, Gilliatt RW (1972) Anatomical changes in pe- ripheral nerves compressed by a pneumatic tourniquet. J Anat 113:433−455

Olsson Y (1975) Vascular permeability in the peripheral nervous system. In: Dyck PJ, Thomas PK, Lambert EH (eds) Peripheral neuropathy. Saunders, Philadelphia, Pa., pp 190−200 Prineas J, Spencer PS (1975) Pathology of the nerve cell body

in disorders of the peripheral nervous system. In: Dyck PJ, Thomas PK, Lambert EH (eds) Peripheral neuropathy, vol 1.

Saunders, Philadelphia, Pa., pp 253−295

Schröder JM (1985) Degeneration und Regeneration nach Plexus- brachialis-Verletzung. In: Hase U, Reulen H-J (eds) Läsionen des Plexus brachialis. De Gruyter, Berlin, pp 65−70

Schröder JM (1999) Pathologie des Nervensystems VIII. Patholo- gie peripherer Nerven. In: Doerr W, Uehlinger E (eds) Spezi- elle pathologische Anatomie, vol 13/VIII. Springer, Berlin Hei- delberg New York

Seddon HJ (1975) Surgical disorders of the peripheral nerves.

Churchill Livingstone, Edinburgh

Seitz RJ, Reiners K, Himmelmannn F, Heininger K, Hartung HP, Toyka KV (1989) The blood-nerve barrier in Wallerian de- generation: a sequential long-term study. Muscle Nerve 12:627−635

Stöhr M (ed) (1980) Iatrogene Nervenläsionen. Thieme, Stuttgart Webster HD (1962) Schwann cell alterations in metachromatic

leukodystrophy: preliminary phase and electron microscopic observations. J Neuropathol Exp Neurol 21:534−554